may 13–16, 2015 · le centre sheraton hotel, 1201 boulevard rené–lévesque west, montreal, qc...

Le Centre Sheraton Hotel, 1201 Boulevard René–Lévesque West, Montreal, QC

May 13–16, 2015

SCIENTIFIC PROGRAM

CBMTG HEAD OFFICE • Malachite Management, Inc. • Suite 400, 570 West 7th Avenue, Vancouver, BC, V5Z 1B3

T. 604.874.4944 F. 604.874.4378 Email: cbmtg@malachite–mgmt.com Web: www.cbmtg.org

ANNUAL CONFERENCE OF THE CANADIAN BLOOD AND MARROW TRANSPLANT GROUP

CBMTG HEAD OFFICESuite 400, 570 West 7th Avenue, Vancouver, BC, V5Z 1B3T: 604-874-4944 • F: 604-874-4378 • E: [email protected] • W: www.cbmtg.org 2

May 13-16, 2015

SCIENTIFIC PROGRAM


Mot du premier ministre / Welcome from the premierAu nom du gouvernement du Québec, c’est avec plaisir que je transmets mes salutations à tous les participantes et participants à la conférence annuelle de la Société canadienne de greffe de cellules souches hématopoïétiques.

Le Québec est fier d’accueillir à Montréal cet événement majeur dans le milieu médical. C’est grâce à des rendez-vous comme celui-ci, qui constituent d’importants lieux d’échanges d’informations, de connaissances et d’expériences entre experts et intervenants dans le domaine de la greffe de moelle osseuse, que l’on peut améliorer les soins et les traitements aux patients, donner un élan à la recherche en repoussant toujours les limites de la science.

Je salue cette mission des plus méritoires que poursuit, au nom de la santé publique, la Société canadienne de greffe de cellules souches hématopoïétiques, et je lève mon chapeau à vous tous ici qui y contribuez de façon exceptionnelle.

Je vous souhaite une excellente conférence et un séjour des plus agréables dans la métropole du Québec.

On behalf of the Québec government, it is with pleasure that I extend my greetings to all participants in the annual conference of the Canadian Blood and Marrow Transplant Group. (CBMTG)

Québec is proud to host this major medical conference in Montréal. It is through gatherings such as this one, which facilitate significant exchanges of information, knowledge and experience between experts and interveners in the field of bone marrow transplant, that we can improve care and treatment for patients and spur research by constantly expanding the horizons of science.

I would like to pay tribute to this praiseworthy public health mission that the Canadian Blood and Marrow Transplant Group is pursuing and congratulate all of you here who are achieving this goal in a remarkable manner.

I extend my best wishes for an excellent conference and a pleasant stay in Montréal.

Philippe Couillard

SCIENTIFIC PROGRAM

3Le Centre Sheraton

Montreal HotelMay 13-16, 2015

Table of Contents

Welcome Messages ............................................................................. 4

Board of Directors and Conference Planning Committee ...................... 5

Accreditation ...................................................................................... 5

Disclosures ......................................................................................... 6

Invited Speakers, Chairs, and Panelists ................................................ 7

Conference App ................................................................................. 8

Social Event Information ..................................................................... 8

Conference-at-a-Glance ...................................................................... 9

CBMTG Committee and Special Interest Group Meetings ................... 13

Session Summaries ........................................................................... 14

Oral Abstracts Index ......................................................................... 21

Oral Abstract Summaries .................................................................. 21

Poster Abstracts Index ...................................................................... 26

Poster Abstract Summaries ............................................................... 29

Le Sheraton Montreal Floor Plan ....................................................... 58

About CBMTG .................................................................................. 59


May 13-16, 2015

SCIENTIFIC PROGRAM


A message from the CBMTG presidentDear Colleagues,

On behalf of the Board of Directors I am happy to welcome you to the Canadian Blood and Marrow Transplant Group (CBMTG) 2015 Annual Conference!

The conference planning committee, led by Dr. Silvy Lachance, has worked hard to put together a scientific program addressing topics of interest to all disciplines in the field of blood and marrow transplantation. I think you will agree, they have been very successful.

I encourage you to participate in as many activities as possible while at the conference. In particular, I wish to highlight a few CBMTG events that we wish all members would support:

1. CBMTG Town Hall: As you know, last year CBMTG conducted a strategic plan. There we determined to strengthen our education, research, fundraising, and advocacy initiatives. Now we need your help to develop what our programs and services will look like over the next few years. Please join us! We will be providing good company, food and drink!

2. Annual General Meeting: The annual general meeting of the CBMTG will be held on Friday, May 15, 2015 from 10:15am to 11:15am. At this meeting we hear reports on the activities of the association for the last year, recognize awardees and craft the direction for our future.

3. CBMTG Social Event: Please join me and your colleagues to celebrate! The social is a time for you to network, get to know your colleagues better and experience some Montreal Joie de Vivre!

Enjoy the meeting.

Sincerely,

Christopher Bredeson, MD, MSc, FRCPC

President, Canadian Blood and Marrow Transplant Group

A message from the conference chairDear Colleagues,

On behalf of the conference planning committee and the Montreal BMT community, I am pleased to welcome you to beautiful Montreal.

The conference planning committee has worked hard over the past year to put together an exciting program that informs on the latest research and breakthroughs in blood and marrow transplant, and that is of interest to the multidisciplinary BMT community. We are proud to welcome speakers from across the country and the world here to share their expertise. I hope that you will find our conference to be a valuable learning and networking experience.

I suggest you take the time to experience our wonderful city throughout the long weekend. Montreal is famous for its French culture, food, inspired by the cuisine of its diverse ethnic communities, elegant boutiques, vibrant downtown area, and beautiful sites. Montreal manages to be relaxed but vibrant and has a joie-de-vivre that is impossible to resist.

Enjoy the conference. Enjoy your stay.

Sincerely,

Silvy Lachance, MD, FRCPC, CSPQ

Conference Chair

SCIENTIFIC PROGRAM

5Le Centre Sheraton


Conference Planning CommitteeChair: Silvy Lachance, MD, FRCPC, CSPQ

Committee members:

• Imran Ahmad, MD • Stephen Couban, MD, FRCPC • Matthew Seftel, MD, MPH, MRCP, FRCPC

• Naheed Alam, MD • Lisa Martin, MLT, CQE • Pierre Teira, MD

• Christopher Bredeson, MD, MSc, FRCPC • Gizelle Popradi, MD, FRCPC • Marie-France Vachon, RN, MScN, CPON, CSIO, CHTC

AccreditationThe CPASS of the Faculty of Medicine of the University of Montreal is fully accredited by the Association of Faculties of Medicine of Canada (AFMC) and from the Quebec College of Physicians.

This activity, approved by the CPASS of the University of Montreal, is an Accredited Group Learning Activity under Section 1, as defined by the Maintenance of Certification program of the Royal College of Physicians and Surgeons of Canada for a maximum of 13.75 hours.

Participants must claim the number of hours according to their participation.

CBMTG Board of Directors

President-Elect, Andrew Daly, MDCM, FRCPC

Past President, Silvy Lachance, MD, FRCPC, CSPQ

President, Christopher Bredeson,

MD, MSc, FRCPC

Secretary, Jennifer Wiernikowski,

MN, NP-Adult, CON(C)

Director-at-Large, Research

Donna Wall,MD

Director-at-Large, Education

Naheed Alam,MD

Treasurer, Raewyn Broady,

MBChB, FRACP, FRCPA, FRCPC


May 13-16, 2015

SCIENTIFIC PROGRAM


DisclosuresPhilippe Bouchard, Speaker

• Advisory Board – EUSA Pharma, Merck

Christopher Bredeson, Speaker, Planning Committee Member

• Advisory Board – Celgene, Sanofi, Otsuka• Research Support – Celgene, Sanofi, Otsuka• Unrestricted Educational Grant – Celgene, Sanofi, Otsuka,

Hoffman-La Roche, Seattle Genetics, Lundbeck• Honoraria – Celgene, Sanofi, Otsuka, Jazz Pharmaceuticals

Rena Buckstein, Speaker

• Research Funds – Celgene• Honoraria – Celgene, Novartis

Stephen Couban, Planning Committee Member

• Advisor – Seattle Genetics, Novartis, Sanofi, Janssen, Bristol-Myers Squibb

Corey Cutler, Speaker

• Consultant – Takeda/Milennium, Celgene, Pharmacyclics, Onyx, Immucor, Fate, Idera, Bristol-Myers Squibb, Sandoz Bio-Oncology

Massimo Dominici, Speaker

• Research Funds – Chiesi Spa, Fresenius Hemocare Srl, Kaneka Corporation, Lipogems SpA

• Financial Interest – RigeneranD Srl

Stephan Grupp, Speaker

• Research Support – Novartis• Consultant – Novartis

Silvy Lachance, Planning Committee Member

• Speaker – Sanofi • Advisory Board – Sanofi, GLyPharma Therapeutics,

Hoffman-La Roche

Paul Martin, Speaker

• Advisory Board – Pharmacyclics, Pfizer• Consultant – Enlivex Therapeutics, Janssen

Thomas Nevill, Speaker

• Speaker – Novartis, Celgene, Alexion• Advisory Board – Celgene, Alexion• Research Grant – Celgene, Alexion

Denis-Claude Roy, Speaker

• Grant Support - Kiadis Pharma

Kirk R. Schultz, Speaker

• DSMB member – Juno Therapeutics, Mesoblast• Unrestricted research funding – Genzyme• Meeting support – Jazz Pharmaceuticals, EUSA Pharma, Medac

Matthew Seftel, Planning Committee Member

• Advisory Board – Lundbeck, Merck• Speaker – Celgene, Novartis

Donald Vinh, Speaker

• Advisor – CSL Behring, Pfizer• Speaker – CSL Behring • Research Grant – CSL Behring, Astellas

Marcel van den Brink, Speaker

• Consultant – Merck, Boehringer Ingelheim• Speaker – Merck, Novartis, Boehringer Ingelheim, Regeneron• Advisory Board – Novartis, Boehringer Ingelheim, Tobira

Therapeutics

SCIENTIFIC PROGRAM

7Le Centre Sheraton


Invited Speakers, Chairs, and PanelistsImran Ahmad, MD, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

David Barth, MD, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

Philippe Bouchard, BPharm, MSc, BCOP, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Christopher Bredeson, MD, MSc, FRCPC, The Ottawa Hospital, Ottawa, ON, Canada

Rena Buckstein, MD, FRCPC, Odette Cancer Centre, Toronto, ON, Canada

Stephan Busque, MD, MSc, FRCSC, Stanford School of Medicine, Stanford, CA, USA

Sandra Cohen, MD, FRCPC, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Stephen Couban, MD, FRCPC, QEII Health Sciences Centre, Halifax, NS, Canada

Corey Cutler, MD, MPH, FRCPC, Dana Farber Cancer Institute, Boston, MA, USA

Kevin Dawe, CCPA, MPAS, BSc, CancerCare Manitoba, Winnipeg, MB, Canada

Minh-Quan Do, Transplant Patient, Student, Montreal, PQ, Canada

Massimo Dominici, MD, University Hospital of Modena and Reggio Emilia, Modena, Italy

Geneviève Dorval, MSc candidate, Department of Anthropology, University of Montreal, Montreal, PQ, Canada

Michel Duval, MD, University of Montreal, Montreal, PQ, Canada

Heidi Elmoazzen, PhD, Canadian Blood Services, Ottawa, ON, Canada

Sylvie Fortin, PhD, Department of Anthropology, University of Montreal, Montreal, PQ, Canada

Stephan Grupp, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

Mike Halpenny, MLT (CMLTD), Canadian Blood Services, Ottawa, ON, Canada

Marie-Josée Hébert, MD, FRCPC, Canadian National Transplant Research Program, University of Montreal, Montreal, PQ, Canada

Silvy Lachance, MD, FRCPC, CSPQ, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Paul Martin, MD, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Lisa Martin, MLT, CQE, Canadian Blood Services, Ottawa, ON, Canada

Marie-Christine Meunier, PhD, D(ABHI), Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Kelly Murphy, MLT, MSc, Canadian Blood Services, Edmonton Stem Cell Centre, Edmonton, AB, Canada

Thomas Nevill, MD, FRCPC, Leukemia/Bone Marrow Transplant Program of BC, Vancouver, BC, Canada

Claude Perreault, MD, FCAHS, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, PQ, Canada

Gizelle Popradi, MD, FRCPC, Royal Victoria Hospital, Montreal, PQ, Canada

Eileen Quinlan, RN, SCM, National Public Cord Blood Bank, Brampton Civic Hospital, Brampton, ON, Canada

Vanderson Rocha, MD, PhD, Churchill Hospital, Oxford, UK

Denis-Claude Roy, MD, Hôpital Maisonneuve-Rosemont, Montreal, PQ, Canada

Guy Sauvageau, MD, PhD, FRCPC, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, PQ, Canada

Kirk R. Schultz, MD, B.C. Children’s Hospital, Vancouver, BC, Canada

Matthew Seftel, MD, MPH, MRCP, FRCPC, CancerCare Manitoba, Winnipeg, MB, Canada

Bronwen Shaw, MD, PhD, Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI, USA

John Storring, MD, CM, McGill University Health Centre, Montreal, PQ, Canada

D. Robert Sutherland, PhD, Princess Margaret Cancer Centre, Toronto, ON, Canada

Pierre Teira, MD, MSc, CHU Sainte Justine, Montreal, PQ, Canada

Marie-France Vachon, RN, MScN, CPON, CSIO, CHTC, CHU Sainte-Justine, Montreal, PQ, Canada

Marcel van den Brink, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Donald Vinh, MD, McGill University Health Centre, Montreal, PQ, Canada

Peter Zandstra, PhD, FRSC, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada

May 13-16, 2015CBMTG HEAD OFFICESuite 400, 570 West 7th Avenue, Vancouver, BC, V5Z 1B3T: 604-874-4944 • F: 604-874-4378 • E: [email protected] • W: www.cbmtg.org 8

May 13-16, 2015

SCIENTIFIC PROGRAM


Introducing the CBMTG 2015 Conference App!

Did you know that there is a conference app

that you can download that lists all of the session

information, speakers, speaker bio’s, abstracts,

venue maps, and other important conference

information?

Download the app onto your iPhone, iPad,

Android, or Blackberry by scanning the QR

code below or searching for “CBMTG” in your

phone’s app store.

Social Event InformationFRIDAY, MAY 15, 2015 • 7:00PM – 11:30PM

Montreal Science Centre2 Rue de la Commune Ouest, Montréal, QC H2Y 4B2

Registration:

Tickets are free of charge for all full conference delegates, though pre-registration is required. Guest tickets may be purchased from the CBMTG Head Office. The registration deadline is Sunday, May 10, 2015.

Transportation:

Transportation has been arranged to bring delegates from the conference hotel to the social event venue. The first shuttle will depart from the hotel lobby at 6:45pm. The last shuttle will depart at 7:15pm.

Returning from the Montreal Science Centre, shuttles will leave beginning at 9:00pm, with the last shuttle departing at 11:45pm.

The Montreal Science Centre is approximately a 25 minute walk from Le Centre Sheraton Montreal Hotel. Directions are available at the registration desk.

SCIENTIFIC PROGRAM

9Le Centre Sheraton

Montreal HotelMay 13-16, 2015May 13-16, 2015

Conference at a glance *All rooms are on the fourth floor, unless otherwise specified

WEDNESDAY, MAY 13, 2015

4:00pm – 7:00pm Conference Registration COAT CHECK/VESTIAIRE

4:00pm – 7:00pm Speaker Services SALON 8

7:00pm – 8:30pm

Nursing Networking SessionFacilitators: Jennifer Wiernikowski, MN, NP-Adult, CON(C), Marie-France Vachon, RN, MScN, CPON, CON(C), CHTC

MUSSET, LEVEL A

THURSDAY, MAY 14, 2015

7:00am – 7:00pm Conference Registration COAT CHECK/VESTIAIRE

7:00am – 6:00pm Speaker Services SALON 8

7:00am – 8:45am Symposium 1: Breakfast BALLROOM/SALLE DE BAL

9:00am – 10:00am

Session 1: Canadian Blood and Marrow Transplant Group (CBMTG) – Canadian National Transplant Research Program (CNTRP) Joint SessionChair: Silvy Lachance, MD, FRCPC, CSPQ

CNTRP Update Marie-Josée Hébert, MD, FRCPC

Renal and Hematopoietic Cell Transplant for Tolerance InductionStephan Busque, MD, MSc, FRCSC

BALLROOM/SALLE DE BAL

10:00am – 10:15am Health Break with Exhibits BALLROOM WEST/ SALLE DE BAL OUEST

10:15am – 11:45am

Session 2: Graft-Versus-Host DiseaseChairs: Imran Ahmad, MD, Gizelle Popradi, MD, FRCPC

HANS MESSNER LECTURESHIPNIH Consensus on Chronic GVHD at 10 Years: Looking Back and Looking Forward Paul Martin, MD

ECP Canadian Experience David Barth, MD


12:00pm – 1:30pm Symposium 2: Lunch BALLROOM/SALLE DE BAL

1:45pm – 2:45pm

Session 3: Transplant from the Donor PerspectiveChair: Matthew Seftel, MD, MPH, MRCP, FRCPC

Donor Selection and Safety Bronwen Shaw, MD


2:45pm – 3:00pmHealth Break and Poster Group 1 PresentationsHealth break located in Ballroom West/Salle de bal ouest. Poster group presentations located in Ballroom Foyer/Foyer salle de bal.


May 13-16, 2015

SCIENTIFIC PROGRAM


THURSDAY, MAY 14, 2015

3:00pm – 4:30pm

Session 4A: BMT 101Chair: Philippe Bouchard, BPharm, MSc, BCOP

Picking the Conditioning Regimen for Allogeneic Transplants: A Peek Behind Oscar Zoroaster’s Curtain Christopher Bredeson, MD, MSc, FRCPC

Updates in CMV Donald Vinh, MD

Non-Carmustine-Containing Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Lymphoma Philippe Bouchard, BPharm, MSc, BCOP


Session 4B: NursingChair: Marie-France Vachon, RN, MScN, CPON, CON(C), CHTC

Myeloablative and Reduced Intensity Conditioning Marie-France Vachon, RN, MScN, CPON, CSIO, CHTC

Encounters with Death and Loss Sylvie Fortin, PhD, Geneviève Dorval, MSc Candidate

Transitioning from a Pediatric Transplant Centre to an Adult Transplant Centre: What Patients Have to Say! Minh-Quan Do

SALON 6/7, LEVEL 3

Session 4C: Laboratory TechnologistsChair: Lisa Martin, MLT, CQE

New HLA Typing Technologies Marie-Christine Meunier, PhD

Replacement of Pentaspan and Management of Critical Supplies Lisa Martin, MLT, CQE

Experience Changing from Pentaspan to Hespan for Cord Blood Processing Heidi Elmoazzen, PhD

Replacement for Pentaspan in Cryopreservation Solutions used for Hematopoietic Progenitor Cell Products Mike Halpenny, MLT

CD34 Enumeration of Thawed HPCs: Is it Worth it? Kelly Murphy, MLT, MSc

Post-Thaw CD34+: To Test or Not to Test? D. Robert Sutherland, PhD

DRUMMOND WEST/ OUEST, LEVEL 3

4:45pm – 5:45pmSession 5: Oral Abstract PresentationsChairs: Christopher Bredeson, MD, MS, FRCPC, Stephen Couban, MD, FRCPCFor more information, see page 21.


5:45pm – 6:45pm Welcome Reception with Exhibits BALLROOM WEST/ SALLE DE BAL OUEST

7:00pm – 9:00pmCBMTG Town HallFacilitated by the CBMTG Board of DirectorsDinner will be provided.


SCIENTIFIC PROGRAM

11Le Centre Sheraton


FRIDAY, MAY 15, 2015



7:00am – 8:45am Symposium 3: Breakfast BALLROOM/SALLE DE BAL

9:00am – 10:00am

Session 6: Canadian Blood and Marrow Transplant Group (CBMTG) – International Society for Cellular Therapy (ISCT) Joint SessionChair: Denis-Claude Roy, MD

Understanding Stem Cells Aging as a Platform to Enhance Tissue Regeneration Massimo Dominici, MD, ISCT President


10:00am – 10:15amHealth Break and Poster Group 2 PresentationsHealth break located in Ballroom West/Salle de bal ouest. Poster group presentations located in Ballroom Foyer/Foyer salle de bal.

10:15am – 11:15am Annual General Meeting BALLROOM/SALLE DE BAL

11:30am – 1:00pm Symposium 4: Lunch BALLROOM/SALLE DE BAL

1:15pm – 3:15pm

Session 7: Myelodysplastic SyndromeChair: John Storring, MD

Debate: “MDS should be treated prior to transplant”

FOR THE RESOLUTION: Rena Buckstein, MD, FRCPC

AGAINST THE RESOLUTION: Thomas Nevill, MD, FRCPC

How to Optimize Allogeneic Hematopoietic Cell Transplant for High Risk Patients with MDS Corey Cutler, MD, MPH


3:15pm – 3:30pmHealth Break and Poster Group 3 PresentationsHealth break located in Ballroom West/Salle de bal ouest. Poster group presentations located in Ballroom Foyer/Foyer salle de bal.

3:30pm – 5:00pm Clinical Trials Network and BMT Registry MeetingChairs: Kristjan Paulson, MD, Donna Wall, MD


5:00pm – 6:00pm

Session 8: Fred Saunders LectureshipChair: Pierre Teira, MD, MSc

Cell Therapy for ALL Crosses the Activity Threshold Stephan Grupp, MD, PhD


7:00pm – 11:30pm Social EventSee details on page 8

MONTREAL SCIENCE CENTRE

May 13-16, 2015CBMTG HEAD OFFICESuite 400, 570 West 7th Avenue, Vancouver, BC, V5Z 1B3T: 604-874-4944 • F: 604-874-4378 • E: [email protected] • W: www.cbmtg.org 12

May 13-16, 2015

SCIENTIFIC PROGRAM


SATURDAY, MAY 16, 2015



8:00am – 9:00am Continental Breakfast BALLROOM/SALLE DE BAL

9:00am – 12:00pm

Session 9: Cord Blood Chair: Sandra Cohen, MD, FRCPC

UM171: From Bench to Bedside Guy Sauvageau, MD, PhD

Engineering Control into Clinical Human Blood Stem Cell Expansion Technologies Peter Zandstra, PhD, FRSC

The Canadian Experience in Cord Blood Transplantation Michel Duval, MD

10:45am – 11:00am: Health Break

Which are the Criteria for Selecting Double Cord Blood Units for Adults? Vanderson Rocha, MD, PhD


10:45am – 11:00amHealth Break and Poster Group 4 PresentationsHealth break located in Ballroom West/Salle de bal ouest. Poster group presentations located in Ballroom Foyer/Foyer salle de bal.

12:15pm – 1:45pm Symposium 6: Lunch BALLROOM/SALLE DE BAL

2:00pm – 3:00pm

Session 10: Till and McCulloch LectureshipChair: Claude Perreault, MD, FCAHS

The Importance of Thymic Function in Allogeneic SCT Marcel van den Brink, MD, PhD


3:00pm – 3:30pm Closing Remarks BALLROOM/SALLE DE BAL

3:00pm – 6:00pmHéma Québec Wet LabMeet in Le Centre Sheraton Montreal lobby at 2:00pmFor more information see page 13

HÉMA-QUÉBEC STEM CELL LABORATORY

SCIENTIFIC PROGRAM


Montreal HotelMay 13-16, 2015May 13-16, 2015

CBMTG Committee and Special Interest Group Meetings

Nursing Networking Session WEDNESDAY, MAY 13, 2015, 7:00PM – 8:30PM

Musset, Level A

The CBMTG has heard from its nurse members that an opportunity to network and learn from one another would be of great value. The CBMTG is happy to invite all BMT nurses to attend a networking and social event.

Join us to connect with other transplant nurses, transplant nurse co-ordinators, Nurse Practitioners, and Clinical Nurse Specialists. Round tables will be set up to try to help you find nurses with similar roles and light facilitation of the evening by Jennifer Wiernikowski, NP and Marie-France Vachon, RN will highlight the work and direction of CBMTG with a focus on the needs of nurse members.

Join us for wine, cheese and networking in Montreal!

CBMTG Town HallTHURSDAY, MAY 14, 2015, 7:00PM – 9:00PM

Ballroom/Salle de bal

Please join your BMT colleagues from across Canada at the CBMTG Town Hall. In the first meeting of its kind, CBMTG will be holding a session to help shape the future of our association. We will be brainstorming around the key issues facing the organization over food and wine.

All CBMTG members are invited and encouraged to attend this event.

CBMTG Annual General MeetingFRIDAY, MAY 14, 2015, 10:15AM – 11:15AM


The CBMTG Board of Directors invites all CBMTG members to attend this meeting. We will hear reports on the activities of the association over the last year and craft the direction for our future.

Clinical Trials Network and BMT RegistryFRIDAY, MAY 15, 2015, 3:30PM – 5:00PM


Dr. Donna Wall, Chair of the CBMTG-CTN, will discuss current projects of the CBMTG-CTN as well as the future of the network.

Dr. Kristjan Paulson, Lead of the CBMTG National Registry, will discuss the current status of the registry as well as upcoming projects.

All CBMTG members are invited to attend this session.

Laboratory Committee MeetingSATURDAY, MAY 16, 2015, 8:00AM – 9:00AM

Salon 7

The laboratory technologist special interest group is a networking/re-source opportunity for laboratory professionals. It focuses on technical and regulatory issues. The group currently has 40 members from across Canada and continues to grow along with the CBMTG.

All laboratory technologist conference delegates are invited to join this special interest group and attend this face-to-face meeting at the annual conference.


May 13-16, 2015

SCIENTIFIC PROGRAM


Session Summaries

SESSION 1: CANDIAN BLOOD AND MARROW TRANSPLANT GROUP (CBMTG) AND CANADIAN NATIONAL TRANSPLANT RESEARCH PROGRAM (CNTRP) JOINT SESSION

THURSDAY, MAY 14, 2015 | 9:00AM - 10:00AM

RENAL AND HEMATOPOIETIC CELL TRANSPLANT FOR TOLERANCE INDUCTION

Stephan Busque, MD, MSc, FRCSC, Stanford School of Medicine, Stanford, CA, USA

Tolerance induction after organ transplantation has the potential not

only to free patients from the side effects of immunosuppressive drugs

but also to prevent chronic rejection and therefore increase graft and

patient survival. Three pioneer centers, MGH-Harvard, Stanford and

Northwestern, have developed clinical protocols to achieve tolerance

after kidney transplantation after decades of preclinical work. At the

core of all these protocols is the combination of donor hematopoietic

cell infusion along with the transplanted organ. Transient or stable,

mixed or complete chimerism has been achieved and patients have

been weaned off successfully of their immunosuppressive medication

for years with normal kidney function. The presentation will review

these protocols in regard of their conditioning regimen and results.

SESSION 2: GRAFT-VERSUS-HOST DISEASE

THURSDAY, MAY 14, 2015 | 10:15AM - 11:45AM

NIH CONSENSUS ON CHRONIC GVHD AT 10 YEARS: LOOKING BACK AND LOOKING FORWARD

Hans Messner Lectureship

Paul Martin, MD, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

During the past year, the NIH consensus development conference

project on criteria for clinical trials in chronic graft-versus-host disease

completed an update of the original landmark work from a decade ago.

The diagnosis and staging working group clarified the overlap chronic

GVHD subcategory and the distinction between active disease and past

tissue damage and revised the diagnostic criteria for involvement of

mouth, eyes, genitalia, and lungs. Final histological diagnostic catego-

ries have been simplified from 4 categories to 3: “no GVHD,” “possible

GVHD,” and “likely GVHD,” based on better reproducibility achieved

by combining the previous categories of “consistent with GVHD” and

“definite GVHD” into the single category of “likely” GVHD. To date, no

diagnostic, prognostic or predictive chronic GVHD biomarkers have

been qualified for clinical applications. The biomarker working group

provided a four-part framework for biomarker investigations: identifica-

tion, verification, qualification, and clinical application based on regu-

latory standards. The supportive care working group summarized new

information regarding the prevention and management of infections,

and common complications of chronic GVHD, and offered recommen-

dations for patient education, preventive measures, and appropriate

follow-up. Major changes in recommended response criteria include

elimination of several clinical parameters from the determination of re-

sponse, updates to or addition of new organ scales to assess response,

and the recognition that minimal, clinically insignificant worsening that

does not usually warrant a change in therapy should not be classified

as progression. Major issues for clinical trials include the definition of

eligibility criteria, the development, validation and selection of primary

and secondary endpoints, and the mapping of an overall approach that

could support regulatory review. Development of an optimal primary

endpoint demonstrating clinical benefit is an urgent unmet need in the

field. The advances gained from this update have prepared the field for

more rapid translation of laboratory discoveries into clinical practice.

ECP CANADIAN EXPERIENCE

David Barth, MD, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

Please see the program updates or conference app for more information regarding this session.

SCIENTIFIC PROGRAM



SESSION 3: TRANSPLANT FROM THE DONOR PERSPECTIVE

THURSDAY, MAY 14, 2015 | 1:45PM – 2:45PM

DONOR SELECTION AND SAFETY

Bronwen Shaw, MD, PhD, Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI, USA

The focus of this talk will be to explore all aspects of hematopoietic cell

transplantation donor management and care, both in the unrelated and

related donor setting. Although stem cell donation is very safe overall

there are well recognized adverse reactions. Many of these are highly

predictable and short lived (e.g. back or bone pain, nausea, flu-like

symptoms) and appropriate counseling of the donors can ensure a

problem free recovery. We and others have shown that there are several

demographic and social factors which predict for delayed recovery (e.g.

gender, QoL measures), and efforts to stratify donor care at an indi-

vidual donor level based on these risks can be made.

Uncommonly, serious and even life threatening adverse reactions can

occur in donors, and our role is to minimize these wherever possible.

Unrelated donors are assessed using internationally agreed suitabil-

ity guidelines which aim to remove any increased risk. In many cases

the selection of related donors does not follow similar strict suitability

guidelines and several publications and studies have shown an increase

in adverse events in related donors with significant co-morbidities.

Efforts to address these discrepancies in care are being undertaken in-

ternationally by several organizations.

Centralized reporting of adverse reactions is important for the field to

identify trends and investigate new phenomena. The World Marrow

Donor Association curates a centralized reporting system for unrelated

donors. Some efforts are underway to create parallel reporting in related

donors, through organizations such as the European Blood and Marrow

Transplantation Group and the WHO. These and other organizations

collaborate with regulatory bodies such as FACT to raise the profile of

donor care and management.

SESSION 4A: BMT 101


PICKING THE CONDITIONING REGIMEN FOR ALLOGENEIC TRANSPLANTS: A PEEK BEHIND OSCAR ZOROASTER’S CURTAIN

Christopher Bredeson, MD, MSc, FRCPC, The Ottawa Hospital, Ottawa, ON, Canada

Allogeneic transplantation is a complicated amalgam of science and

art. The transplant team must balance donor issues, disease charac-

teristics, available graft source, and the conditioning regimen. Once a

patient has been identified, the variable that the transplant team has

the most influence over is the conditioning regimen. Over the last ~15

years new ideas and approaches have been introduced; all with fanfare,

not all with success. So just what goes into picking the magic elixir

that makes up the conditioning regimen? The answer lies behind the

wizard’s curtain and we are going to peek.

UPDATES IN CMV

Donald Vinh, MD, McGill University Health Centre, Montreal, PC, Canada

Cytomegalovirus (CMV) infection and disease remain significant com-

plications in adult recipients of hematopoietic stem cell transplantation

(HSCT). This session will provide an overview of the relevant epidemi-

ology, microbiology, and immunobiology of CMV in HSCT; review the

various methodologies in use for monitoring and diagnosis; and discuss

anti-viral and immunological approaches to management.

NON-CARMUSTINE-CONTAINING CONDITIONING REGIMENS FOR AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION IN LYMPHOMA

Philippe Bouchard, BPharm, MSc, BCOP, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Carmustine is a chemotherapy agent widely used as part of preparative

regimens for autologous hematopoietic cell transplantation for lympho-

ma such as BEAM and BEAC. The availability of carmustine in Canada

has been an issue in recent years. Alternative conditioning regimens

not containing carmustine include other myeloablative agents such as

busulfan. The literature for non-carmustine containing regimens is re-

viewed to discuss these alternative preparative regimens.


May 13-16, 2015

SCIENTIFIC PROGRAM


SESSION 4B: NURSING


MYELOABLATIVE AND REDUCED INTENSITY CONDITIONING

Marie-France Vachon, RN, MScN, CPON, CSIO, CHTC, CHU Sainte-Justine, Montreal, PC, Canada

Over the years, the increase in knowledge around hematopoietic stem

cell transplantation has allowed to extend the transplant indications to

various populations, especially in older patients and those affected by a

non-malignant disease. The arrival of newer chemotherapies (ex. Fluda-

rabine) and monoclonal antibodies (ex. Alemtuzumab) have greatly

participated in the development of novative protocols called reduced

intensity. The myeloablative protocols have classically been developed

with the objective of destroying the whole bone marrow for essentially

three reasons: a) make space for the donor cells, b) destroy the recipient

immune system; and in the cases of malignant diseases, c) get rid of

the malignant cells. Those protocols also come with short term toxicities

on various organs (heart, kidneys, liver) bringing significant morbidities

and mortalities. Consequently, for some patients, a transplant will not

be an option due to the very high risks associated. Also, some patients

have non-malignant diseases that do not necessarily need to have a

complete destruction of the bone marrow to obtain a cure. It is well

known that the cohabitation of the donor and recipient bone marrow

(mixed chimerism) can be possible in those circumstances. Therefore,

the use of reduced intensity protocols makes this process of tolerance

possible and will reduce the risk of short term toxicities and also the risk

of long term toxicities such as infertility and secondary cancer. When

choosing between a myeloablative or a reduced intensity protocol, we

should also take in consideration the impact it will have on the choice of

graft, the cellularity, the risk of GVHD and rejection. In summary, the de-

velopment of new conditioning regimens has broadened our horizons

and offered a new hope of recovery for more patients.

ENCOUNTERS WITH DEATH AND LOSS

Sylvie Fortin, PhD, Department of Anthropology, University of Montreal, Montreal, PQ, Canada

Geneviève Dorval, MSc Candidate, Department of Anthropology, University of Montreal, Montreal, PQ, Canada

Health care providers thrive to enhance their patients’ well being. They

nevertheless encounter paths that lead to loss and death. In contem-

porary medicine (and in technologically invested environments such

as many of our hospital units today) this death is often one that is

decided upon. Such decisions are complex amongst health care teams

and between providers, patients and families. Stemming from anthro-

pological research carried out in different Canadian hospital settings

on broader issues related to clinical practice today (neonatal, pediatric

hematology-oncology, PICU) we will address death and loss as it crosses

our data, revealing an array of norms and values – shared and conflict-

ing- as well as different perspectives on cure and care issues.

TRANSITIONING FROM A PEDIATRIC TRANSPLANT CENTRE TO AN ADULT TRANSPLANT CENTRE: WHAT PATIENTS HAVE TO SAY!

Minh-Quan Do, Transplant Patient, Student, Montreal, PQ, Canada

During this presentation I will describe my experiences moving from the

pediatric transplant centre at CHU Sainte-Justine, Montreal to the adult

transplant centre at Maisonneuve Rosemont Hospital, Montreal. I will

describe my expectations during the transition, as well as what I have

liked and disliked about my experiences at the two institutions.

SESSION 4C: LABORATORY TECHNOLOGISTS

THURSDAY, MAY 14, 2015 |3:00PM – 4:30PM

NEW HLA TYPING TECHNOLOGIES

Marie-Christine Meunier, PhD, Hôpital Maisonneuve Rosemont, Montreal, PQ, Canada

Every day, new HLA alleles are discovered and HLA typing methods are

constantly evolving.

The HLA laboratory needs to be able to cope with this ever changing

reality and offer clinicians and patients the best HLA and histocompat-

ibility typing options for their clinical protocols. The choice of typing

method will always depend on the type of transplant unit (bone marrow

versus solid organ), the time allowed to perform typing, and the level of

HLA typing resolution that is clinically needed. From serological, to real

time PCR, to PCR-SSP, to sequence based typing (SBT) or next genera-

tion sequencing (NGS), each typing method has advantages and brings

new challenges to the laboratory.

SCIENTIFIC PROGRAM



REPLACEMENT OF PENTASPAN AND MANAGEMENT OF CRITICAL SUPPLIES

Lisa Martin, MLT, CQE, Canadian Blood Services, Ottawa, ON, Canada

Over the past few years there have been several critical reagents and

supplies used by the cell therapy community that have been discon-

tinued or no longer available for sale in Canada, such as Pentaspan,

Baxter bottles, and cryocyte bags. My presentation will discuss the re-

placement of Pentaspan, but will also discuss the preparation involved

in supply management to insure suitable replacements are always iden-

tified and ready in the event critical reagents and supplies are no longer

available.

EXPERIENCE CHANGING FROM PENTASPAN TO HESPAN FOR CORD BLOOD PROCESSING

Heidi Elmoazzen, PhD, Canadian Blood Services, Ottawa, ON, Canada

Canadian Blood Services is building a national public cord blood bank.

On September 30, 2013, the National Public Cord Blood Bank began

banking cord blood units for transplant purposes. When the cord blood

bank began, cord blood units were originally processed on the Sepax 2

automated cell processing system using Pentaspan. In 2014, Pentaspan

was no longer available in Canada and the National Public Cord Blood

Bank switched over to processing using Hespan. An overview of the

National Public Cord Blood Bank experience from switching starches

will be provided.

REPLACEMENT FOR PENTASPAN IN CRYOPRESERVATION SOLUTIONS USED FOR HEMATOPOIETIC PROGENITOR CELL PRODUCTS

Mike Halpenny, MLT (CMLTD), Canadian Blood Services, Ottawa, ON, Canada

Replacement of any critical reagent in the manufacturing process for

hematopoietic progenitor cell products requires significant efforts in

planning and executing the validation and qualification process. Cana-

dian Blood Services Stem Cell Manufacturing and Hospital Services will

describe their efforts/challenges in designing and executing a qualifica-

tion process for the replacement of Pentaspan with Hespan used in the

cryopreservation process for HPC products.

CD34 ENUMERATION OF THAWED HPCS: IS IT WORTH IT?

Kelly Murphy, MLT, MSc, Canadian Blood Services, Edmonton Stem Cell Centre, Edmonton, AB, Canada

The Edmonton stem cell lab has been successfully performing post-thaw

testing on autologous HPC-apheresis products for well over 10 years.

Our program has established a minimum recommended post-thaw dose

for timely engraftment, and endpoints for acceptable post-thaw recov-

ery which may be indicative of impaired cell function. This presentation

will include a number of examples in which the Edmonton stem cell

program has benefited by having the ability to reliably test frozen pilot

samples for viable CD34+ HPCs.

POST-THAW CD34+: TO TEST OR NOT TO TEST?

D. Robert Sutherland, PhD, Princess Margaret Cancer Centre, Toronto, ON, Canada


SESSION 5: ORAL ABSTRACT PRESENTATIONS


For more information regarding the oral abstract presentations please see page 21.

SESSION 6: CANADIAN BLOOD AND MARROW TRANSPLANT GROUP (CBMTG) AND INTERNATIONAL SOCIETY FOR CELLULAR THERAPY (ISCT) JOINT SESSION

FRIDAY, MAY 15, 2015 | 9:00AM – 10:00AM

UNDERSTANDING STEM CELLS AGING AS A PLATFORM TO ENHANCE TISSUE REGENERATION

Massimo Dominici, MD, University Hospital of Modena and Reggio Emilia, Modena, Italy

Human aging is associated with a decrease in tissue functions com-

bined with a decline in stem cells frequency and activity followed by

a loss of regenerative capacity. The molecular mechanisms behind this

senescence remain largely obscure, precluding targeted approaches to

counteract aging. Focusing on mesenchymal stromal/stem cells (MSC),


May 13-16, 2015

SCIENTIFIC PROGRAM


as known adult progenitors, we identified specific switches in gene

expression during aging correlating them with MSC biological fea-

tures. We then selectively forced gene expression observing significant

changes in cell growth, senescence, and differentiation. These findings

indicated master factors driving progenitors behavior lifetime, providing

a better understanding of tissue senescence and leading to optimiza-

tion of MSC performance in cellular therapies.

SESSION 7: MYELODYSPLASTIC SYNDROME

FRIDAY, MAY 15, 2015 | 1:15PM – 3:15PM

DEBATE: “MDS SHOULD BE TREATED PRIOR TO TRANSPLANT”

For the resolution: Rena Buckstein, MD, FRCPC, Odette Cancer Centre, Toronto, ON, Canada

“Victorious warriors win first and then go to war, while defeated war-

riors go to war first and then seek to win.”

In this debate, Dr. Buckstein will review the evidence that justifies ‘de-

bulking’ therapy in high risk MDS prior to allogeneic stem cell transplant

as a means of blast reduction and the establishment of chemosensitivity

and why hypomethylating agents may be particularly advantageous for

logistical and scientific reasons.

Against the resolution: Thomas Nevill, MD, FRCPC, Leukemia/Bone Marrow Transplant Program of BC, Vancouver, BC, Canada

There remains some controversy regarding the need to treat myelo-

dysplastic syndrome (MDS) prior to allogeneic stem cell transplanta-

tion (SCT). Stem cell transplantation is not generally recommended for

patients with IPSS/IPSS-RA “lower-risk” MDS although molecular ge-

netics may influence this decision in the future. At the present time,

management of such patients with ESAs, immunosuppressive therapy

or Lenalidomide is often appropriate but may compromise the success

of future SCT. For patients with higher-risk MDS, cytoreductive therapy

may reduce the burden of disease but has not been convincingly dem-

onstrated to improve outcomes with subsequent SCT. Patients who are

refractory to (or relapse soon after) the cytoreductive treatment and for

those experiencing complications with this therapy, it simply may not

be possible to proceed with transplantation. A careful evaluation of the

risks and benefits of pre-SCT therapy must be a part of the transplanta-

tion algorithm for patients with MDS.

HOW TO OPTIMIZE ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT FOR HIGH RISK PATIENTS WITH MDS

Corey Cutler, MD, MPH, FRCPC, Dana Farber Cancer Institute, Boston, MA, USA

Allogeneic hematopoietic stem cell transplantation for myelodysplastic

syndrome (MDS) is a potentially curative procedure, albeit at significant

risk of morbidity and mortality. With the recent approval of disease-

modifying agents, the appropriate timing of allogeneic HSCT needs

to be addressed. Similarly, the optimal use of these disease modifying

agents prior to HSCT needs to be determined. Patient selection is also

of paramount importance to optimize outcomes. Timing transplantation

correctly, and the choice of the appropriate patient will be discussed.

SESSION 8: FRED SAUNDERS LECTURESHIP

FRIDAY, MAY 15, 2015 | 5:00PM – 6:00PM

CELL THERAPY FOR ALL CROSSES THE ACTIVITY THRESHOLD

Stephan Grupp, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

Chimeric antigen receptors (CARs) combine a binding fragment (scFv)

of an antibody with intracellular signaling domains. We have previously

reported on CTL019 cell therapy expressing an anti-CD19 CAR. Infusion

of these cells results in 100 to 100,000x in vivo proliferation, durable

anti-tumor activity, and prolonged persistence in patients with B cell

tumors, including sustained CRs in adults and children with acute lym-

phoblastic leukemia (ALL; Grupp et al., NEJM 2013, Maude et al., NEJM

2014). My talk will update the audience on ongoing pediatric CTL019

trials.

Relapsed/refractory leukemia, especially refractory disease, ALL in

adults, and relapses after stem cell transplant, pose substantial chal-

lenges, with very little progress made in more than a decade. Targeted

immunotherapy using CAR-modified T cells has emerged as a potent

therapy with an innovative mechanism. Supraphysiologic T cell prolif-

eration, a hallmark of active, T cell-engaging therapies, contributes to

both efficacy and risk. The most notable toxicity is cytokine release syn-

SCIENTIFIC PROGRAM



drome (CRS), which poses a unique challenge for toxicity management.

CTL019 cells can undergo robust in-vivo expansion and can persist for

over two years in patients with relapsed ALL, allowing for the possibil-

ity of long-term disease response without subsequent therapy such as

SCT. This approach also has promise as a salvage therapy for patients

who relapse after allo-SCT with a low risk of GVHD. CTL019 therapy is

associated with a significant CRS that responds rapidly to IL6-targeted

anti-cytokine treatment. CTL019 cells can induce potent and durable

responses for patients with relapsed/refractory ALL. CTL019 therapy has

received Breakthrough Therapy designation from the FDA in both pedi-

atric and adult ALL, and phase II multicenter trials have been initiated.

SESSION 9: CORD BLOOD

SATURDAY, MAY 16, 2015 | 9:00AM – 12:00PM

UM171: FROM BENCH TO BEDSIDE

Guy Sauvageau, MD, PhD, FRCPC, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, PQ, Canada

In this presentation we will provide an overview on how we character-

ized a small molecule that expands human hematopoietic stem cells,

from the discovery to the first clinical trial.

ENGINEERING CONTROL INTO CLINICAL HUMAN BLOOD STEM CELL EXPANSION TECHNOLOGIES

Peter Zandstra, PhD, FRSC, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada

We have developed a robust closed-system bioprocess that combines

a “fed-batch” (FB) media dilution strategy with a first-in-class hema-

topoietic stem cell (HSC) stimulating small molecule (called UM171) to

expand functional umbilical cord blood (UCB)-derived HSCs and pro-

genitors to clinically relevant levels. The feasibility, safety and efficacy

of our FB+UM171-expanded cells for adult allogeneic transplantation

are being tested in a funded Phase I/II clinical trial based at the Hôpital

Maisonneuve-Rosemont in Montreal. In this presentation we will review

our development work to generate robust procedures for clinical blood

cell manufacturing and provide insight into the development of our

next-generation bioprocesses that will enable personalized, cost-effec-

tive, and automated blood progenitors cell production in centres across

Canada.

THE CANADIAN EXPERIENCE IN CORD BLOOD TRANSPLANTATION

Michel Duval, MD, University of Montreal, Montreal, PQ, Canada

This presentation will focus on two topics. First, the Canadian expe-

rience of cord blood transplantation will be described, thanks to the

CBMTG registry. The main discoveries of Canadian investigators in

cord blood transplantation will then be explored, to finally examine

the current ongoing and future research on cord blood transplantation

carried out by Canadian investigators.

WHICH ARE THE CRITERIA OF SELECTING DOUBLE CORD BLOOD UNITS FOR ADULTS?

Vanderson Rocha, MD, PhD, Churchill Hospital, Oxford, UK

Most of adults are transplanted with double unrelated CBUs. Some

studies with small series of patients have tried to establish criteria for

CBU selection for double UCBT (DUCBT).

With the aim to study the impact of cell dose, HLA and other related

factors in a large series of DUCBT recipients, we have conducted a pre-

liminary retrospective based registry study on adults with malignancies

receiving a DUCBT in EBMT centers, with available data on cell dose

and HLA. Number of HLA disparities was determined according to the

unit with the highest degree of mismatches, based on low resolution

typing for HLA-A and -B and high resolution typing for –DRB1. 934

adults met the eligibility criteria for the study: 55% had acute leuke-

mia, 21% lymphoid mature malignancies, 10% MDS and 14% MPD

and multiple myeloma. Median age at DUCBT was 47 years (18-72),

median weight was 71 kg (40-151), and the median time from diag-

nosis to transplantation was 17 months (2-300). Conditioning regimen

was myeloablative in 32% of the patients. ATG was used in 24% of

the cases. GVHD prophylaxis consisted mostly in CSA associated with

MMF. Median number of TNC at collection and infusion were 4.9 x107/

kg (n=934) and 3.6x107/kg (n=735), respectively. Median number of

collected and infused CD34+ cells were 1.9x105/kg (n=818) and 1.6

x105/kg (n=695), respectively. Considering the CBU with the highest

HLA disparity, only 1% of the patients were transplanted with 2 CBUs

6/6, 26% with at least one CBU 5/6, 67% with at least one CBU 4/6

and 6% with at least one CBU 3/6. ABO match was also classified ac-

cording to the CBU with the highest incompatibility with the recipient.

18% of the patients received 2 ABO compatible CBUs, 30% had at

least one CBU with minor ABO incompatibility and 52% received at


May 13-16, 2015

SCIENTIFIC PROGRAM


least one CBU with a major ABO incompatibility. Results: At day 60,

estimated neutrophil recovery was 87%; at day 100, the incidence of

acute GVHD grade 2-4 was 42% and 3-4 was 20%. At 2 years NRM

was 35%, relapse incidence was 20% and overall survival was 47%.

The number of HLA disparities and ABO matching were factors associ-

ated with survival. OS at 2 years was 45% for patients transplanted

with at least one 3/6 or 4/6 CBU, and 54% for those transplanted with

6/6 or at least one 5/6 CBU (p=0.009). At 2 years, OS was 60% for

patients transplanted with ABO compatible units, 47% for those trans-

planted with an ABO minor incompatibility and 45% for major ABO

incompatibility (p=0.008). In multivariate analysis, factors associated

with improved survival were younger age (p=0.01), early disease status

at transplant (p=0.002), absence of ATG in the conditioning regimen

(p<0.001), ABO compatibility (p=0.02) and higher HLA compatibility

(p=0.04). In conclusion, this preliminary restrospective based registry

analysis suggests that ABO and HLA compatibility are important criteria

for CBUs selection for adults undergoing DUCBT. If confirmed, these

criteria should be included in the selection algorithm for CB units in this

transplant setting.

SESSION 10: TILL AND MCCULLOCH LECTURESHIP

SATURDAY, MAY 16, 2015 | 2:00PM – 3:00PM

THE IMPORTANCE OF THYMIC FUNCTION IN ALLOGENEIC SCT

Marcel van den Brink, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, USA


Héma-Québec Wet Lab

SATURDAY, MAY 16, 2015 | 3:00PM – 6:00PM

Héma-Québec, Stem Cells Laboratory, 4045 Côte-Vertu, St. Laurent

Try a validated, FDA approved cytometry technique for the enumera-

tion of CD34 cells in post-thaw cord blood samples. Principles of the

technique will be explained/revised. A procedure will be provided to

participants along with cryopreserved CBU samples. Samples (cryotubes

or segments) will be thawed according to a modified Rubinstein proce-

dure. Labeling will be done using a BD stem cell enumeration kit and

acquisition will be performed using an Accuri C6 cytometer. Results will

be calculated, compared, and discussed. The workshop will be followed

by a question and answer session and dinner.

All laboratory technologists/assistants who test the viability of thawed

CBUs are invited to attend this session.

Héma Québec has arranged transportation to and from this session for

all participants. Participants are to meet in the lobby of Le Centre Shera-

ton Montreal Hotel at 2:00pm.

SCIENTIFIC PROGRAM



Oral Abstract IndexTHURSDAY, MAY 14, 2015 | 4:45PM – 5:45PM

# Title Topic Presenting Author

01DONOR LYMPHOCYTES DEPLETED OF ALLOREACTIVE T-CELLS PROVIDE IMMUNE PROTECTION WITHOUT CAUSING GRAFT- VERSUS-HOST DISEASE

Clinical: Clinical Trials/Observations

Denis-Claude Roy, MD

02

FAVORABLE RESULTS OF HAPLOIDENTICAL STEM CELL TRANSPLAN-TATION FOLLOWED BY INJECTION OF DONOR T-CELLS SELECTIVELY PHOTODEPLETED OF THEIR ANTI-RECIPIENT FRACTION: INTERIM RESULTS FROM A PHASE 2 TRIAL IN PATIENTS WITH AML, ALL, AND MDS

Clinical: Clinical Trials/Observations

Denis-Claude Roy, MD

03UMBILICAL CORD BLOOD COLLECTION: FIRST YEAR OPERATIONS AT THE CANADIAN BLOOD SERVICES, NATIONAL PUBLIC CORD BLOOD BANK

Clinical: Laboratory/Quality Eileen Quinlan, RN, SCM

04FRAILTY IN PRE-HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) PATIENTS: A PILOT STUDY ASSESSING THE FEASIBILITY OF CONDUCT-ING A SCORING MEASUREMENT IN THE OUTPATIENT SETTING

Clinical: Pharmacy, Nursing, and Laboratory

Kevin Dawe, BSc

05CHRONIC GRAFT-VERSUS-HOST DISEASE BIOMARKER DISCOVERY AND REPLICATION: CXCL10 + CXCL9 PROVIDES THE HIGHEST DIAG-NOSTIC VALUE IN ADULTS

Research: Basic/Translational

Kirk R. Schultz, MD

01. DONOR LYMPHOCYTES DEPLETED OF ALLOREACTIVE T-CELLS PROVIDE IMMUNE PROTECTION WITHOUT CAUSING GRAFT-VERSUS-HOST DISEASE

Roy DC,1,2 Lachance S,1,2 Cohen S,1,2 Kiss T,1,2 Sauvageau G,1,2 Busque L,1,2 Delisle JS, 1,2 Guérin M,1 SidiBoumédine R,1 Ahmad I,1 Guertin MC,3 Wagena E,4 Ruediger M,4 Selleslag D,5 Lewalle P,6 Maertens J,7 Laport G,8 Rezvani K,9 Negrin R, 8 Velardi A,10 Mielke S,11 Barrett AJ,12 Perreault C,1,2 and Roy J1,2

1Division of Hematology-Oncology/Stem Cell Transplantation, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada; 2Department of Medicine, University of Montreal, Montreal, Canada; 3Department of Biostatistics, Montreal Health Innovations Coordinating Center, Montreal, Canada; 4Kiadis Pharma, Amsterdam, The Netherlands; 5Department of Hematology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium; 6Department of Hematology, Jules Bordet Institute, ULB, Brussels, Belgium; 7Department of Hematology, Stem cell transplantation unit, Catholic University of Leuven, Leuven, Belgium; 8Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, U.S.A.; 9Department of Stem Cell Transplant and Cellular Therapy, University of Texas, M.D.Anderson Cancer Center, Houston, U.S.A.; 10Division of Hematology and Clinical Immunology, University of Perugia, Italy; 11Stem Cell Therapy Center, Wuerzburg, Germany; 12National Institute of Health, Bethesda, MD, U.S.A.

Background: The intensive T-cell depletion of the graft accompany-ing haploidentical stem cell transplantation (SCT) delays immune re-constitution and results in frequent and rapidly lethal infectious com-

plications. The ability to accelerate immune reconstitution following HLA-haploidentical-SCT would extend safe transplantation to the large number of patients who do not have an HLA-matched donor.

Methods: Twenty-seven adults with very high-risk malignancy entered a Phase I clinical trial of haplo-identical T-cell depleted allogeneic SCT followed by the infusion of Alloreactive T-lymphocyte depleted cells ImmunoTherapy (ATIR) to prevent graft-versus-host disease (GVHD). Selective elimination of host-reactive T cells was achieved using a di-bromorhodamine-based photodepletion approach. All stem cell grafts underwent in vitro immunomagnetic T cell depletion using CD34+ posi-tive cell selection (Miltenyi). The myeloablative regimen consisted of TBI (1200 cGy), thiotepa (5 mg/kg), ATG (12.5 mg/kg) and fludarabine (200 mg/m2). No GVHD prophylaxis was administered.

Results: Eight patients were removed from the study because of leukemia relapse (n=4) or late identification of an unrelated donor (n=4). All 8 patients died. Nineteen patients (11 M, 8 F) with very high-risk hematologic malignancies, mostly refractory or relapsed AML(10), MDS(4) and biphenotypic leukemia(1), CLL(2), CML(1) and NHL(1) pro-ceeded with the trial. Median age was 54 years (range: 20-62). Increas-


May 13-16, 2015

SCIENTIFIC PROGRAM


ing doses of ATIR from 1x104 to 5x106 CD3 cells/kg were infused at a median of 30 days (28-39) after SCT. Greater than 90% of activated (CD25+CD44+) CD4 and CD8 T cells (p<0.004) and anti-host cyto-toxic T lymphocyte precursors (CTLp) (p=0.0008) were depleted from the donor lymphocyte infusions (DLI). Interferon-γ responses against CMV, EBV and Influenza peptides were maintained post-photodeple-tion. Naive (T

Naive) and central memory (T

CM) T cells were also preserved,

but mature effector memory populations (TEMRA

) decreased after photo-depletion. All patients showed complete donor chimerism and durable hematologic engraftment. No patients developed grade III-IV acute GVHD. Acute GVHD grade II developed in 4 patients at a median of 102 days post-transplant (range 45-125). Five patients developed de novo chronic GVHD at a median of 4.8 months post-transplant. All patients responded rapidly to oral immunosuppression lasting for a median of 6.3 months. Patients administered the highest T-cell doses (2.0-5.0x106

CD3 cells/kg) showed earlier reconstitution of CD3, CD4 and CD8 cells (all p≤0.02). Time to the first infection was delayed in patients receiving high ATIR doses (p=0.015). During the first 6 months post-ATIR, the number of patients without infections was only 1 (14%) of the 7 low T-cell doses patients but increased to 8 (67%) in the high T-cell dose group (p=0.027). The overall survival was 47.4±22.4% (±95% confi-dence interval) and the event-free-survival 36.8±21.7% at 2 years, with a median follow-up of survivors of 5.0 years. This strategy resulted in lower treatment-related mortality (p<005) compared to a group of con-temporaneous controls (n=61 patients) receiving the same treatment without photodepleted cells and improved survival (p<005), particularly in high cell-dose ATIR recipients.

Conclusions: Post-transplant immunotherapy with photodepleted DLI decreased the incidence and severity of infections without inducing severe GVHD. These results document the benefits of administrating selectively depleted T-cells after haploidentical transplantation.

02. FAVORABLE RESULTS OF HAPLOIDENTICAL STEM CELL TRANSPLANTATION FOLLOWED BY INJECTION OF DONOR T-CELLS SELECTIVELY PHOTODEPLETED OF THEIR ANTI-RECIPIENT FRACTION: INTERIM RESULTS FROM A PHASE 2 TRIAL IN PATIENTS WITH AML, ALL, AND MDS

Roy DC,1 Maertens J,2 Walker I,3 Lachance S,1 Roy J,1 Cohen S,1 Kiss T,1 Foley SR,3 Lewalle P,4 Selleslag DLD,5 DeJong L,6 Velthuis JHL,6 Gerez L,6 Reitsma K,6 Rovers J,6 and Mielke S7

1Department of Hematology and Cellular Therapy Laboratory, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, QC, Canada; 2Department of Hematology, University Hospital Gasthuisberg Leuven, Leuven, Belgium; 3Department of Medicine, Juravinski Hospital and Cancer Centre, Hamilton, Canada; 4Experimental Laboratory of Hematology, Institut Jules Bordet, ULB, Brussels, Belgium; 5Department of Hematology, Az Sint-Jan, Brugge, Belgium; 6Kiadis Pharma, Amsterdam-Duivendrecht, Netherlands; 7Zentrum Innere Medizin (ZIM), Abteilung Hämatologie und Onkologie, Universitätsklinikum Würzburg, Wurzburg, Germany Research support by Kiadis Pharma.

Introduction: For patients in need of a hematopoietic stem cell trans-plant (HSCT) but lacking an HLA matched donor, a haploidentical family donor is a particularly appealing alternative. However, to prevent graft-versus-host disease (GVHD), haploidentical HSCT necessitates intensive in vivo or ex vivo T-cell depletion that results in frequent and often lethal infectious complications and/or high relapse rates, thus decreas-ing overall survival. To overcome this limitation, we have developed a strategy that photodepletes host-reactive cells from the donor T cell graft, while preserving anti-infection and anti-leukemia reactivity.

Patients and Methods: In an open-label, multi-centre phase 2 clini-cal trial (CR-AIR-007; NCT01794299), 12 of a planned 23 patients with high-risk hematologic malignancies were treated to date with this im-munotherapy approach consisting of donor lymphocytes selectively al-lodepleted of host-reactive T-cells using photodynamic therapy (ATIR). ATIR was infused 28-32 days after haploidentical CD34-selected HSCT. No post-transplant GVHD prophylaxis was used.

Results: Twelve patients, mean age of 45 (range 21-64), 6 females/6 males with AML (n=9) and ALL (n=3) were treated with ATIR so far. ATIR consisted mainly of T-cells (>90%), with residual B and NK cells (≤10%). Selective depletion of recipient-reactivity in each ATIR cell graft was assessed using a CFSE-based proliferation assay. Cell division numbers upon stimulation were analyzed using Modfit LT software (Fig 1A), which generated a proliferation index representing viable/reactive T-cells in donor cells (blue) and final ATIR product (green)(Fig 1B). Selec-tive depletion of recipient-reactive T-cells with preservation of reactivity towards 3rd party antigens and anti-CD3/CD28 was observed in all ATIR cell grafts and used as release criteria.

SCIENTIFIC PROGRAM



Figure 1: A) CFSE-dilution pattern in Modfit LT software of ATIR stimulated with 3rd party cells. B) CFSE-based proliferation confirmed selective deple-tion of recipient-reactive T-cells in all grafts (representative depiction).

Preparative regimen consisted of A) FTBI (1200 cGy; n=5) or B) melpha-lan (120 mg/m2; n=7), along with thiotepa (10 mg/kg), fludarabine (30 mg/m2 x5 d) and ATG (2.5 mg/kg x4 d). Neutrophil and platelet engraft-ment was achieved in all patients at a median of 12 days (range: 9-35). No patient experienced graft rejection. Two patients developed acute GVHD grade I (skin only) approximately 130 days post HSCT, which was of short duration, (18 and 41 days). Two patients died of infection and no patient relapsed at a mean follow-up of 8 months post HSCT (range 1-14 months). Treatment related mortality (TRM) is 20% and overall survival (OS) is 80% at 9 months post-transplant.

Conclusions: These data confirm that a novel immunotherapy strategy consisting of donor lymphocytes selectively photodepleted of alloreac-tive cells (ATIR) can be manufactured consistently and reproducibly. Results to date show that ATIR is safe and does not cause any grade III/IV GvHD. Moreover, haploidentical HSCT patients treated with ATIR demonstrate very promising TRM and OS rates.

03. UMBILICAL CORD BLOOD COLLECTION: FIRST YEAR OPERATIONS AT THE CANADIAN BLOOD SERVICES, NATIONAL PUBLIC CORD BLOOD BANK

Elmoazzen H, Mostert K, Halpenny M, Yang LCanadian Blood Services, Ottawa, Ontario

Background: Successful cord blood (CB) stem cell transplantation is directly associated with the quantity and potency of stem cells harvest-ed in a CB unit. Two parameters commonly used to evaluate a CB unit include the total volume and total nucleated cell counts (TNCs). Obtain-ing high quality CB units at time of collection is a main focus in CB banking and the first step for transplant success. The Canadian Blood Services, National Public Cord Blood Bank (NPCBB) initiated operations as of September 30, 2013.

Study Design and Methods: Collection process development result-ed in both ex utero and in utero collection methods implemented at the NPCBB. A collection kit was developed in house containing the CB collection bag (MSC1208DU, Macopharma®). The two needle collec-tion bag and its double packaging system is manufactured and vali-dated to meet GMP and ISO standards to ensure safe, consistent and reliable cord blood collection performance. Following informed consent from donors, CB units were collected according to established SOPs by appropriately trained workers using both in utero and ex utero collection methods. Retrospective review was performed on CB units collected in the first 12 months of operations at the NPCBB. Quality collection parameters included; collection volume, TNC and microbial contamination.

Results: A total of 2,068 CB units were collected between September 30, 2013 and September 29, 2014. 1348 (65.2%) and 720 (34.8%) CB units were collected using ex utero and in utero collection methods, respectively. The NPCBB developed acceptance criteria to determine eli-gible/bankable CB units: Collection volume >40ml, TNC > 1.3x109 for ethnically diverse and >1.5x109 for Caucasian. As a result, a CB unit eligibility rate of 25.67% (n=346) for ex utero collection and 28.75% (n=207) for in utero collection was observed. Mean volume and TNC counts were 85.03±31.94 ml, 1.09x109±0.53 for in ex utero collec-tions and 96.61±32.92 ml, and 1.19x109±0.66 for in utero collec-tions. In addition, microbial contamination was tested on 553 quali-fying CB units using an in-house validated BacT/ALERTmethod. Our results demonstrated a microbial contamination rate of 0.29% (n=1) in ex utero collections and 2.42% (n=5) for in utero collections.

Summary: Our results indicate the feasibility of using the NPCBB col-lection kit, including the Macopharma® collection bag to collect CB units that meet high quality acceptance criteria. Collection data from both collection methods, ex utero vs in utero, allows for a direct com-parison between methods and will allow further analysis with post CB unit production and post-transplant data in the future. The data dem-onstrates our collection process results in a low contamination rate in total qualifying CB units collected. The in utero method resulted in the majority of contamination identified.


May 13-16, 2015

SCIENTIFIC PROGRAM


04. FRAILTY IN PRE-HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) PATIENTS: A PILOT STUDY ASSESSING THE FEASIBILITY OF CONDUCTING A SCORING MEASUREMENT IN THE OUTPATIENT SETTING

Dawe K,1,2 PA, Richardson E,1 CRT, Robinson T,1 RN MN, Szwajcer D,1,3 MD, Wall D,1,4 MD 1 Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, Winnipeg, MB, Canada. 2 Department of Physician Assistant Studies, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada. 3 Department of Medical Oncology and Hematology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada. 4 Department of Pediatrics and Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada

Background: The Manitoba Blood and Marrow Transplant program uses an upper age cut off of 70 years in the setting of a good per-formance status to assess transplant suitability. Our comorbidity as-sessment tools do not reflect patient frailty. We have developed a pragmatic, brief pre-transplant frailty measure which was tested in the outpatient setting.

Methods: Patients referred to the Leukemia/Bone Marrow Transplant clinic for consideration of HSCT who were >60 years of age were ap-proached to participate in the University of Manitoba Research Ethics Board approved study. The frailty assessment consists of (i) asking the patient about unintentional weight loss and mobility challenges (ii) a physical activity questionnaire, (iii) a grip strength test, and (iv) a timed 15 ft. walk. The results were tabulated and categorized as not frail, pre-frail or frail (Fried et al in 2001). The physician also independently cat-egorized the patient as not frail, pre-frail, or frail without access to the frailty index results. The time to complete the assessment was tracked. Agreement between the frailty index and the physician categorization was calculated by the kappa statistic.

Results: 14 patients were accrued to this study with an average age of 67.2 years (60-70 years). All patients had a Karnofsky Performance Score between 80 and 100. Hematopoietic Cell Transplant-Co-morbidity Index scores were 0 (8), 1 (3), 2(1), 3(1), 5(1). Diagnoses included acute leukemia/MDS (7), lymphoma (1), and multiple myeloma (5). Of the 14 patients, 6 patients had autologous transplants, 1 had an allogenic trans-plant, and 7 did not undergo transplant. The time it took the majority of patients to complete the frailty index was between 2-5 minutes. The time it took the nursing assistant to help with the frailty index was between 2-5 minutes. All physicians finished their portion of the study in <2 minutes. The percent agreement between the physician score and the frailty index was 71.4% with a kappa value of 0.48 (See table 1).

TABLE 1 – Frailty index versus physician frailty opinion

Frailty Index Physician Assessment of Frailty

Not Frail 7 9

Pre-Frail 5 5

Frail 2 0

Conclusion: This pilot demonstrates that completion of the frailty index is feasible in an outpatient setting. The index took less than 5 minutes to complete. There was moderate agreement between the physician score and the frailty index. A study of a larger cohort with post-transplant outcome correlation to determine the utility of the frailty index in pre-transplant assessment is in progress.

Reference: Fried, L., Tangen, C., Walston, J., et al. (2001). Frailty in Older Adults: Evidence for a Phenotype. Journal of Gerontology: Medical Science, 56A(3), M146-M156.

05. CHRONIC GRAFT-VERSUS-HOST DISEASE BIOMARKER DISCOVERY AND REPLICATION: CXCL10 + CXCL9 PROVIDES THE HIGHEST DIAGNOSTIC VALUE IN ADULTS

Kariminia A,1 Holton SG,2 Hebert M,3 Martin P,4 Lee S,4 Storek J,5 Couban S,6 Szwajcer D,7 Newell L,8 Walker I,9 Tay J,10 Kuruvilla J,11 Gallagher G,12 Nevill T,13 Toze C,13 Aljurf M,14 Popradi G,15 Lipton J,11 Subrt P,1 Samadi S,1 Sung S,1 Storer B,4 Rozmus J,1 Schultz K1

1 BC Children’s Hospital/University of British Columbia, Vancouver, Canada. 2 University of Minnesota, Blood and Marrow Transplant Program, Minneapolis, USA. 3 CRCHUM, Hopital Notre-Dame-, University of Montreal, Montreal Canada. 4 Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, USA. 5 University of Calgary, Calgary, AB, Canada. 6 Queen Elizabeth II Hospital, Halifax, NS. 7 CancerCare Manitoba, Winnipeg, MB. 8 OHSU Knight Cancer Institute, Portland, OR. 9 Hamilton Health Sciences, Hamilton, ON. 10 Ottawa Hospital, Ottawa, ON. 11 Princess Margaret Cancer Centre, Toronto, ON. 12 CHA Hopital Enfant-Jesus, Quebec City, QC. 13 Leukemia/BMT Program of BC, Vancouver General Hospital, BC Cancer Agency and University of BC, Vancouver, BC. 14 King Faisal, Riyadh, Saudi Arabia. 15 McGill University Health Center, Montreal, QC

Background: Chronic graft-versus-host disease (cGVHD) remains a significant long-term complication after allogeneic blood and marrow transplantation (BMT). Many candidate cGVHD biomarkers have been identified, but none is validated for use in clinical practice.

Methods: We evaluated diagnostic cGVHD biomarkers in a small adult discovery set (N=38, 21 cGVHD within one month of diagnosis and 17 controls) obtained from the Fred Hutchinson Cancer Research Center followed by a replication analysis in a larger primarily CBMTG cohort of 9 CBMTG centres including 2 US, and 1 Saudi Arabian BMT centre (N = 30 cGVHD and 55 controls). Proteomic analysis on plasma was

SCIENTIFIC PROGRAM



performed at the University of Victoria Proteomics Facility (BC, Canada) with MALDI-TOF-TOF methodology using iTRAQ labels. Multiple Reac-tion Monitoring-Mass Spectrometry (MRM) was used to measure 71 candidates identified by proteomic studies. Luminex analysis was done for cytokines previously identified in previous studies. Based on these results, 13 of the most promising markers were tested in an indepen-dent CBMTG cohort of 30 cGVHD and 85 post BMT controls. Cases and controls identified as early (<9 months) and late onset (≥9 months) with early (6 months) and late controls (12 months) and for the presence or absence of previous acute GVHD.

Results: Proteomic analysis of the discovery cohort (N = 38) with con-firmation by MRM revealed two proteins of high interest as cGVHD di-agnostic markers, aminopeptidase N (sCD13, p = 0.004) and Peptidase Inhibitor 16 (PI-16, p = 0.005). Enzymatic studies confirmed higher levels of aminopeptidase N in cGVHD. Results for all 13 candidates are shown in the Table. CXCL10, CXCL9, aminopeptidase N, sBAFF, Gelso-lin, and Endothelin (p <0.0001 – 0.05) were associated with cGVHD with ROC AUCs of 0.77, 0.65, 0.63, 0.67, 0.65, and 0.71. The combi-nation of CXCL10 and CXCL9 gave the highest AUC of 0.83. The impact of previous aGVHD and TBI were evaluated for each marker. TBI was a contributing factor only for endothelin while previous aGVHD did not contribute to any of the markers.

Conclusions: We identified two markers with AUCs >0.70 and 4 can-didates with AUCs >0.63. The optimal combination of CXCL10+CXCL9 had an AUC of 0.83. CXCL10 and CXCL9 are both ligands for CXCR3A and B potentially acting on activated T cells, dendritic cells, NK cells, smooth muscle, epithelial and endothelial cells. Further evaluation on whether these diagnostic markers can be used as prognostic or predic-tive markers is needed.

TABLE 1 – Univariate replication results for 13 candidate biomarkers

Candidate biomarkers

N evaluable

Effect size1

P-value AUC

IL-8 85 0.9x 0.77

sCD13 Aminopeptidase N

85 1.3x 0.02 0.63

IL-2R 85 1.2x 0.16

sBAFF 85 1.4x 0.01 0.67

CXCL10 85 3.9x <0.0001 0.77

PI-16 85 85 0.8x 0.13

ICAM-1 85 1.3x 0.15

CXCL9 85 1.8x 0.05 0.65

MCP1 85 1.1x 0.41

Vascular biomarkers

Endothelin 85 0.7x 0.03 0.65

Anti-LG32 85 0.9x 0.75

Gelsolin AGA 85 0.8x 0.002 0.70

Gelsolin HVV 85 0.8x 0.0006 0.71

Kallikrein 85 0.9x 0.44

Combination of markers

CXCL10 + CXCL9 0.83

1Fold difference cGVHD vs. control, 2Anti-LG3 has been associated with renal transplant rejection.


May 13-16, 2015

SCIENTIFIC PROGRAM


Poster Group 1: Clinical Trials and Observations AbstractsTHURSDAY, MAY 14, 2015 | 2:45PM – 3:00PM | BALLROOM FOYER/FOYER SALLE DE BAL

# Abstract Title Presenting Author

1IMPROVED PREDICTION OF CD34+ CELL YIELD PRIOR TO PERIPHERAL BLOOD HEMATOPOIETIC PROGENITOR CELL COLLECTION USING A MODIFIED TARGET VALUE-TAILORED APPROACH

Dawn Sheppard

2RISK FACTORS FOR PROGRESSION FROM CMV VIREMIA TO CMV DISEASE IN ADULT RECIPIENTS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT

Johnathan Mack

3 AUTOLOGOUS STEM CELL TRANSPLANT FOR MYASTHENIA GRAVIS: A SINGLE-CENTRE EXPERIENCE Adam Bryant

4OUTCOMES OF BONE MARROW OR CORD BLOOD MATCHED RELATED TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE: EXPERIENCE OF A CANADIAN CENTRE

Pierre Teira

5LONG TERM REMISSIONS CAN BE OBTAINED AFTER ALLOGENEIC HAEMATOPOETIC CELL TRANSPLANTS IN BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

Uday Deotare

6

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA IN SECOND COMPLETE REMISSION IS ASSOCIATED WITH SIGNIFICANT LONG TERM SURVIVAL AND THE MODIFIED EBMT SCORE PREDICTS NON-RELAPSE MORTALITY IN THIS PATIENT GROUP

Jennifer Frazer

7PREDICTORS OF OVERALL AND PROGRESSION FREE SURVIVAL AFTER RELAPSE FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION FOR HODGKIN LYMPHOMA

Helena Dhamko

8BENEFIT OF SCREENING LUMBAR PUNCTURE PRIOR TO ALLOGENEIC STEM CELL TRANSPLANT IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML)

Laura Anne Habib

9A SCOPING REVIEW OF EVIDENCE FROM RCTS ADDRESSING BEST TRANSFUSION PRACTICES FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Grace Christou

10EVALUATION OF ZOSTER PROPHYLAXIS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION USING VALACYCLOVIR FOLLOWED BY VACCINATION

Kareem Jamani

Poster Group 2: Clinical Trials and Observations AbstractsFRIDAY, MAY 15, 2015 | 10:00PM – 10:15PM | BALLROOM FOYER/FOYER SALLE DE BAL


11OUTCOMES OF MATCHED RELATED AND UNRELATED BONE MARROW TRANSPLANTATION AFTER REDUCED-TOXICITY CONDITIONING FOR CHILDREN SUFFERING FROM CHRONIC GRANULOMATOUS DISEASE

Pierre Teira

12TO PARTNER WITH PATIENTS TO IMPROVE HEMATOPOIETIC CELL TRANSPLANT OUTCOME: IMPLEMENTATION OF A PATIENT PARTNERSHIP PROGRAM WITHIN THE STEM CELL TRANSPLANT UNIT

Francine Grondin

13PROPHYLACTIC ANTIBIOTICS AIMING GUT DECONTAMINATION WORSEN ACUTE GRAFT-VERSUS-HOST DISEASE AND SURVIVAL FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Caroline Letendre

SCIENTIFIC PROGRAM



14EVALUATION AND SYSTEMATIC TREATMENT OF PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (GVHD) IN A SPECIALIZED MULTIDISCIPLINARY OUTPATIENT CLINIC: A 5-YEAR EXPERIENCE

Anish Nair

15DEFIBROTIDE TREATMENT FOR SEVERE HEPATIC VENO-OCCLUSIVE DISEASE: AN ANALYSIS OF CLINICAL BENEFIT AS DETERMINED BY NUMBER NEEDED TO TREAT (NNT) TO ACHIEVE COMPLETE RESPONSE AND IMPROVE SURVIVAL

Kathleen Villa

16OUTCOMES OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT) IN PATIENTS WITH MYELOFIBROSIS (MF) EXPOSED TO JAK1/2 INHIBITORS

Mohamed Shanavas

17IMPACT OF CIPROFLOXACIN PROPHYLAXIS ON ANTIMICROBIAL RESISTANCE IN NEUTROPENIC LEUKEMIA/STEM CELL TRANSPLANT PATIENTS

Dawn Warkentin

18MODERATE/SEVERE GRADE OF CHRONIC GRAFT VERSUS HOST DISEASE AND YOUNGER AGE (LESS THAN 45 YEARS OLD) ARE RISK FACTORS FOR AVASCULAR NECROSIS IN ADULT PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Sita Bhella

19FLAG-IDA AS FRONTLINE INDUCTION OR SALVAGE THERAPY FOR PATIENTS WITH HIGH RISK AND/OR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML)

Sita Bhella

20CLINICAL STUDIES OF EX VIVO EXPANSION OF HEMATOPOIETIC STEM CELLS TO ACCELERATE ENGRAFTMENT AFTER UMBILICAL CORD BLOOD TRANSPLANTATION: A SYSTEMATIC REVIEW

Pauline Damien

21HOSPITALIZATIONS AMONG ADULT SURVIVORS OF CHILDHOOD CANCER TREATED WITH STEM-CELL TRANSPLANTATION

Muhammad Ali

Poster Group 3: Pharmacy, Nursing, and Laboratory AbstractsFRIDAY, MAY 15, 2015 | 3:15PM – 3:30PM | BALLROOM FOYER/FOYER SALLE DE BAL


22 POST-THAW CD34 ENUMERATION: STABILITY OF SAMPLE BEFORE ANALYSIS Carl Simard

23CORD BLOOD THAWING: COMPARISON OF ALTERNATIVE THAWING SOLUTIONS RELATIVE TO DEXTRAN BASED SOLUTION

Carl Simard

24NUMERATION OF COLONY-FORMING UNIT GRANULOCYTE-MACROPHAGE (CFU-GM) COLONIES IN CORD BLOOD USING AN AUTOMATED INSTRUMENT: STEMVISIONTM

Mike Halpenny

25UMBILICAL CORD BLOOD PROCESSING: FIRST YEAR OPERATIONS AT THE CANADIAN BLOOD SERVICES, NATIONAL PUBLIC CORD BLOOD BANK

Mike Halpenny

26CYP2C19*17 GENETIC POLYMORPHISM – AN UNCOMMON CAUSE OF VORICONAZOLE TREATMENT FAILURE

Maheen Abidi

27PUBLIC AND FAMILY CORD BLOOD BANKING: A GOOD QUALITY SAMPLE IS A GOOD QUALITY SAMPLE

Leanne Casbourn

28ICING ORAL MUCOSITIS: ORAL CRYOTHERAPY IN MULTIPLE MYELOMA PATIENTS UNDERGOING AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT

Adrienne Fulford


May 13-16, 2015

SCIENTIFIC PROGRAM


29SECURING INFORMED CONSENT AT STEM CELL DRIVES: A UBC STEM CELL CLUB IMPLEMENTATION OF WORLD MARROW DONOR ASSOCIATION GUIDELINES

Warren Fingrut

30 REDIRECTING INELIGIBLE AND NON-OPTIMAL STEM CELL DONORS TO HELP IN OTHER WAYS Warren Fingrut

31PATIENT’S PERSPECTIVE AND SATISFACTION WITH EMOTIONAL SUPPORT: WHAT DO PATIENT’S WANT?

Georgia Georgiou

32DEVELOPMENT OF A STANDARDIZED FOLLOW UP FOR PEDIATRIC TRANSPLANT LONG TERM SURVIVORS BY FAMILY PHYSICIANS

Jo-Anne Richer

Poster Group 4: Basic and Translational Research AbstractsSATURDAY, MAY 16, 2015 | 10:45AM – 11:00AM | BALLROOM FOYER/FOYER SALLE DE BAL


33PRE-PROCESSING STORAGE TEMPERATURE EFFECTS ON THE POTENCY OF CORD BLOOD STEM CELLS

Cynthia Letarte

34TNC BUT NOT CD34+ CELL RECOVERY IN BUFFY COATS IS INFLUENCED BY THE WAITING TIME BEFORE CORD BLOOD UNIT PROCESSING

Renée Bazin

35DEFINING CATCHMENT AREAS FOR THE ORGANIZATION OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ONTARIO

Jonathan Wang

36 FORECASTING THE DEMAND FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ONTARIO Jonathan Wang

37IN VITRO PRODUCTION OF MEGAKARYOCYTE PROGENITORS FROM NON-QUALIFIED CORD BLOOD UNITS FOR CLINICAL APPLICATIONS

Josée Laganiére

38USE OF STATINS TO AUGMENT PROGENITOR CELL FUNCTION IN PRE-CLINICAL AND CLINICAL STUDIES OF REGENERATIVE THERAPY AND IMMUNE MODULATION: A SYSTEMATIC REVIEW

David Allan

39FUNCTIONAL IMPAIRMENT OF CD8+ T LYMPHOCYTES IN PEDIATRIC RECIPIENTS OF BONE MARROW OR UMBILICAL CORD BLOOD TRANSPLANTATION DURING THE EARLY POST-TRANSPLANT PERIOD

Insaf Salem Fourati

40 FACILITATING CORD BLOOD RESEARCH IN CANADA Mia Golder

41ONEMATCH 2013 RETROSPECTIVE DONOR SELECTION STUDY: HLA MATCH LEVEL, REGISTRY AUTONOMY, AND CORD BLOOD USAGE

Valerie Stewart

SCIENTIFIC PROGRAM



1. IMPROVED PREDICTION OF CD34+ CELL YIELD PRIOR TO PERIPHERAL BLOOD HEMATOPOIETIC PROGENITOR CELL COLLECTION USING A MODIFIED TARGET VALUE-TAILORED APPROACH

Sheppard D,1 Tay J,1 Palmer D,2 Xenocostas A,3 Doulaverakis C,3 Huebsch L,1 McDiarmid S,1 Ranjeeta Mallick,1 Martin L,2 Birch P,2 Hamelin L,1 Allan D,1 Bredeson C1

1Ottawa Hospital Research Institute, 2Canadian Blood Services Stem Cell Processing Laboratory, 3Division of Hematology, London Health Sciences Centre

Background: The most commonly used stem cell source for both au-tologous and allogeneic transplantation is mobilized peripheral blood HPCs collected by apheresis.{Pasquini MC, 2013 #1} In the 1990s, Mit-terer et al. used the correlation between the pre-apheresis peripheral blood CD34+ cell count and the final number of CD34+ cells collected to devise a formula for “target value-tailored” (TVT) apheresis.{Mitterer M, 1996 #2} Using local patient data, the Canadian Blood Services Stem Cell Laboratory has created a similar model in order to determine the blood volume to process during apheresis collection.

Objectives: The objectives of this study were to:

1. Determine the correlation between the number of CD34+ cells pre-dicted by the TVT formula and the actual number of CD34+ cells collected

2. Determine whether the TVT formula remains predictive when applied to an external data set

Methods: All apheresis collections performed at the Ottawa Hospital between January 1, 2003 and December 31, 2011 were reviewed. The primary outcome was the correlation between the number of CD34+ cells predicted by the TVT formula and the actual number of CD34+

cells collected on day 1 of apheresis. For the external data set all au-tologous collections performed at the London Health Sciences Centre between December 1, 2008 and December 1, 2013 were reviewed. The external data set was divided into test and validation sets to determine whether a model could be created to predict the final number of CD34+ cells collected on day 1 based on the pre-apheresis CD34+ count.

Results: A total of 1055 collections were included in the analysis. The Ottawa data set included 815 collections, 639 of which were au-tologous and 176 of which were donors. The patient characteristics are shown in Table 1. Of the autologous collections in Ottawa, 586 (93%) were first collections. In 578 (97%) collections, chemotherapy plus G-CSF was used as the mobilization regimen. In 724 collections (88.8%), only 1 collection day was required to achieve the desired number of CD34+ cells. The TVT estimate was highly predictive of the number of CD34+ cells x 106/kg actually collected on apheresis day 1 (r=0.90, p<0.0001; Figure 1).

The London data set included 240 autologous collections. All mobiliza-tions were with G-CSF alone. For the test set, the pre-collection CD34+ count was highly predictive of the number of CD34+ cells x 106/kg collected on day 1 of apheresis (Figure 2). Applying this model to the validation set, the correlation between the predicted and final and day 1 CD34+ cells x 106/kg count was 0.9186 (p<0.0001).

Conclusions: Using a modified TVT approach, the pre-apheresis CD34+ count can be used to accurately predict the number of CD34+ cells x 106/kg collected on day 1. This approach can be applied at other centres, and for different diseases and mobilization regimens. This method can be used to individualize the blood volume processed and thus optimize resource utilization.

Table 1: Patient Characteristics

n (%) Age, range(years)

Male gender(%)

Prior regimens,median (range)

MM 209 (28%) 56.6 (31.9-70.4) 125 (59.5) 1 (1-4)

Indolent NHL 109 (14%) 52.5 (27.2-69.7) 62 (56.9) 2 (1-4)

Aggressive NHL 223 (29%) 51.4 (14.8-69.8) 140 (62.8) 1 (1-4)

HL 68 (68%) 36.9 (14.3-65.2) 37 (54.4) 1 (1-5)

Other/Unknown* 30 (4%) 37.4 (17.5-62.5) NA 1 (0-4)

All indicates all collections; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; HL, Hodgkin lymphoma; NA, unknown or not available

*Other/Unknown includes solid tumours, autoimmune diseases, and collections for which the diagnosis is unknown or unavailable.


May 13-16, 2015

SCIENTIFIC PROGRAM


Figure 1: TVT predicts CD34+ cells x 106/kg collected on apher-esis day 1

Figure 2: Pre-collection CD34+ count predicts CD34+ cells x 106/kg collected on apheresis day 1

2. RISK FACTORS FOR PROGRESSION FROM CMV VIREMIA TO CMV DISEASE IN ADULT RECIPIENTS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT

Mack J, MD1, Tan X, PhD2, Vinh D, MD3, Popradi G, MDCM4 1McGill Unversity, Montreal, QC, Canada, 2Biostatistics Core Facility, McGill University Health Center, Montreal, QC, Canada, 3Department of Medical Microbiology, McGill University Health Centre, Montreal, QC, Canada, 4Hematology, McGill, MUHC, Montreal, QC, Canada

Introduction: Cytomegalovirus (CMV) causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (allo-HSCT). Factors associated with progression from CMV viremia to CMV disease despite pre-emptive CMV treatment are poorly defined. We sought to identify risk factors among adult allo-HSCT recipients.

Methods: Retrospective single-centre case-control study. The McGill University Health Centre SCT Program database was used to identify adults receiving a first allo-HSCT between January 1, 2006 and Febru-

ary 12, 2013, and who experienced ≥1 episode of CMV viremia de-tected by polymerase chain reaction (PCR). Medical records of cases (CMV disease) and controls (viremia without disease) were reviewed for the following data: characteristics of recipient, donor, stem cell graft, transplant procedure, viremic episodes, steroid use post-transplant, and occurrence of acute and/or chronic GVHD post-transplant. Fisher’s exact test or Wilcoxon Rank Sum test (for categorical and continuous variables, respectively) was used. Variables were selected for multivari-ate analysis using the LASSO approach to logistic regression analysis.

Results: Of 134 allo-HSCTs, 29 (21.6%) patients experienced CMV viremia. Among these patients, median age was 51 years (range 27-67), with 48 episodes of viremia. Nine (31%) viremic patients de-veloped CMV disease.

CMV disease occurred at a median of 124 days post HSCT (range 61-322). Patients with CMV disease had a median of 2 viremic episodes before disease (range 1-4). Disease occurred at a median of 33 days from the start of the last viremic episode, and 75 days from the start of the first episode of viremia.

On univariate analysis, factors associated with progression to CMV disease were: steroid-refractory acute GVHD (60% vs. 20%, p=0.028); number of episodes of viremia >1x103 copies/mL (mean 2.4 vs 1.1, p=0.016); longer duration of viremia (mean 38 vs. 22 days, p=0.01); higher peak viral load (mean 4.49x105 vs. 8.31x103 copies/mL, p<0.001); and failure of pre-emptive ganciclovir therapy (50% vs. 10%, p=0.015). On multivariate analysis, no factors were significantly associ-ated with progression to CMV disease.

CMV-related mortality was 33%. All-cause mortality was significantly higher in patients developing CMV disease (100% vs. 35%, log rank test p=0.0027).

Conclusions: In adult allo-HSCT recipients experiencing ≥1 episode of CMV viremia, we found by univariate analysis that patients who de-veloped CMV disease were more likely to have steroid refractory acute GVHD, more episodes of viremia >1x103 copies/mL, a longer duration of viremia, and to have failed first-line pre-emptive ganciclovir therapy. This study, while limited, suggests that these risk factors may be predic-tive of CMV disease. Larger, prospective studies are needed to confirm these risk factors, some of which may be amenable to more aggressive anti-viral therapy.

SCIENTIFIC PROGRAM



3. AUTOLOGOUS STEM CELL TRANSPLANT FOR MYASTHENIA GRAVIS: A SINGLE-CENTRE EXPERIENCE

Bryant A, Atkins H, Pringle C, Allan D, Anstee G, Bence-Bruckler I, Hamelin L, Hodgins M, Hopkins H, Huebsch L, McDiarmid S, Sabloff M, Sheppard D, Tay J, Bredeson C The Ottawa Hospital, Ottawa, ON Canada

Introduction: Myasthenia Gravis (MG) is an antibody-mediated disease affecting the neuromuscular junction. Despite advances in immune-targeted therapies, a subset of patients demonstrate refractory disease with severe or life-threatening symptoms. Autologous hemato-poietic stem cell transplant (auto-HSCT) has been used to successfully treat a variety of autoimmune neurologic conditions including multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, neuro-myelitis optica, and stiff person syndrome. We report our centre’s expe-rience using auto-HSCT for seven patients with MG.

Results: Seven patients underwent HSCT between 2001 and 2011. In-dication for auto-HSCT was MG in six patients and follicular lymphoma (FL) one patient with coincident active MG. Median ages were 37 years at diagnosis and 43 years at auto-HSCT. Before auto-HSCT, MG sever-ity was graded as moderate (grade III) to life-threatening (grade V) by Myasthenia Gravis Foundation of America (MGFA) clinical classification and was refractory to treatment regimens that included pyridostigmine, steroids, additional immunomodulators, and plasma exchange or in-travenous immunoglobulin (IVIg) in all patients. Prior to auto-HSCT all patients but one had at least one myasthenia-related emergency de-partment visit, hospitalization, ICU admission, or intubation.

All patients underwent stem cell mobilization with cyclophosphamide and granulocyte-colony stimulating factor (GCSF). Stem cell grafts were harvested from peripheral blood and selected for CD34+ cells. Condi-tioning regimens used cyclophosphamide and antithymocyte globulin (ATG) with either total body irradiation (TBI) or busulphan to achieve intense immune ablation except for one patient who received condi-tioning for FL (etoposide, melphalan, TBI).

Median follow-up was 40 months (range 29-149) after auto-HSCT. At last follow-up all patients were classified as complete stable remission by MGFA criteria indicating no MG symptoms and no MG-directed therapy. At 8 months post auto-HSCT, all patients had discontinued immune sup-pression, while one continued low-dose pyridostigmine for 5 years. Six patients had no further hospitalizations or emergency department visits. One patient required hospitalizations in the 18 months after auto-HSCT

but has not been hospitalized for MG for more than 11 years.

Patients were hospitalized for auto-HSCT for a median 30 days. Abso-lute neutrophil count exceeded 0.5 x 109/L on median post HSCT day 11. There were no unexpected inpatient complications, ICU admissions, or regimen-related deaths. In the 2 months following auto-HSCT there were 6 transient viral reactivations in three patients. All of these re-solved with treatment. One patient developed acquired amegakaryocyt-ic thrombocytopenia two years after auto-HSCT and is currently stably controlled with IVIg.

Conclusions: We describe seven patients with refractory MG in whom auto-HSCT was effective at inducing a sustained and complete symptom- and treatment-free remission. The procedure was well toler-ated in all patients, but was characterized by an increased frequency of transient viral reactivation. Our experience demonstrates that where MG disease-related morbidity outweighs the established risks of auto-HSCT, stem cell transplant is a viable and realistic option. The novel application of HSCT for this and other autoimmune conditions is an area that warrants further exploration.

4. OUTCOMES OF BONE MARROW OR CORD BLOOD MATCHED RELATED TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE: EXPERIENCE OF A CANADIAN CENTRE

Teira P, MD, Robitaille N, MD, Pastore Y, MD, Vachon M, MSN, Bittencourt H, MD, Duval M, MDCHU Sainte Justine, Department of Pediatric Hematology-Oncology, University of Montreal, Montreal, QC, Canada

Introduction: Hematopoietic stem cell transplantation (HSCT) still remains the only curative treatment for patients suffering from severe forms of sickle cell disease (SCD). The aim of this study was to review the indications and outcomes of SCD children transplanted with a matched sibling donor at a medium sized pediatric institution in Canada.

Methods: From 2003 to 2014, 17 children received a HSCT at our insti-tution. Data were retrospectively extracted from medical charts.

Results: All children had severe forms of SCD including stroke (3/17), silent strokes (7/17), vasculopathy (5/17), acute chest syndrome (11/17), splenic sequestration (7/17) and recurrent vaso-occlusive crisis requir-ing up to 41 hospital admissions for one patient. Neurocognitive im-pairment was documented for 6 out of 11 children tested. Before HSCT, 15/17 children were treated by programmed blood transfusions and 12/17 received Hydroxyurea. Children transplanted after 2010 tended to be younger and to have less brain damages.


May 13-16, 2015

SCIENTIFIC PROGRAM


The median age at HSCT was 9y (2 to 15y). The myeloablative condi-tioning regimen was based on Busulfan, Cyclophosphamide and rabbit antithymoglobulin. The source of stem cells was a bone marrow for 11 patients and a cord blood for 6.

The median follow-up was 59 months (6m to 136m). All patients en-grafted. Stable mixed chimerism (less than 95% of donor cells) was common (13/17). No patient experienced new onset of SCD complica-tions. Previous organ damages did not progress after HSCT. No grade 2-4 acute graft versus host disease (GVHD) was observed. Extensive chronic GVHD was noted for 2 out of 17 patients and evolved favorably on treatment. At 12 months after HSCT, 10 out of 11 children were free from immunosuppressive drugs. Opportunistic infections were common such as CMV (12/15 at risk) or EBV (13/13 at risk), and evolved favor-ably with or without treatment. One death not related to HSCT occurred 42 months after HSCT. Among 5 evaluable women, 3 transplanted after the age of 11 y have primary amenorrhea, whereas 2 transplanted at 5 and 7y of age have normal puberty.

Conclusion: HSCT with a matched sibling donor is safe and effective to cure SCD whether the graft source is a bone marrow or a cord blood. A younger age at HSCT may enhance the functional prognosis of severe SCD and may decrease the risk of long term gonadal toxicity related to HSCT.

5. LONG TERM REMISSIONS CAN BE OBTAINED AFTER ALLOGENEIC HAEMATOPOETIC CELL TRANSPLANTS IN BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

Deotare U, Loach D, Kim D, Gupta V, Kuruvilla J, Messner H, Lipton JAllogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Background: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a clinically aggressive tumor derived from the precursors of plasma-cytoid dendritic cells (pDC) with a high frequency of primary cutaneous involvement, and dissemination to bone marrow with disease progres-sion. Recent data suggest that BPDCN patients treated with acute lym-phoblastic leukemia (ALL)-type regimens, with or without allogeneic stem cell transplantation, may have a better outcome. There are no published randomized controlled trials evaluating the role of autolo-gous Hematopoietic Cell Transplantation (auto-HCT) or allogeneic (allo-HCT) in patients with BPDCN. No guidelines exists to guide physicians about therapy in BPDCN.

Patients and Methods: This retrospective analysis evaluates the

outcome of 6 patients who were diagnosed with BPDCN and underwent allo-HCT at the Princess Margaret Cancer Centre. Prior to transplant 5 out of 6 patients underwent HyperCVAD as the ALL-type chemotherapy for remission induction. All patients were transplanted in CR1. Cyclophos-phamide/Total Body Irradiation (Cy/TBI) and Fludarabine/Busulphan/Total Body Irradiation(FBT-200) were used as myeloablative (MAC) and reduced intensity conditioning (RIC) respectively. GVHD prophylaxis was cyclospo-rine and mycophenolate in related donors with addition of one dose of Alemtuzumab in unrelated donor transplantation.

Results: Median age was 44 years (range, 25 to 70 years) with female preponderance (2M:4F). The graft source was Peripheral Blood Stem Cells (PBSC) in all patients with sibling donors in 2 and fully matched unrelated donors in remaining patients. There was equal distribution of MAC and RIC transplants.

The median time for neutrophil and platelet engraftment was 13.5 (range, 11-17 days) and 13 days (range, 11-14 days) respectively. Two patients had viral haemorrhagic cystitis and cytomegalovirus reactiva-tion but none of them had any major conditioning related complica-tions. Three out of 6 had evidence of acute Graft Versus Host Disease (aGVHD) with grade III-IV in 2 patients. One patient with grade IV aGVHD of the gut expired due to complication of the same. Three pa-tients developed chronic GVHD with 2 having Pulmonary GVHD. None of the patients relapsed and the median duration of remission was 13 months. The overall survival (OS) was 83% for patients who underwent allogeneic HCT when compared with the historical controls with only chemotherapy group with no survivors.

Conclusions: Although front-line induction chemotherapy with Hy-perCVAD can yield CR, allo-HCT should be performed in first CR for transplant eligible patients, as this appears to be required for long term durable remissions. Collaborative prospective clinical trials are certainly needed to better define the role of allo-HCT in BPDCN. This data is pre-sented to make transplant physicians aware of this rare hematological disorder and to invite them to contribute data for a cross Canada study.

SCIENTIFIC PROGRAM



DOD= Date of DiagnosisDCR= Date of Complete RemissionDOT=Date of TransplantDOF=Last Date of Follow up

DODg= Date of DiagnosisDCR= Date of Complete RemissionDOR=Date of RelapseDODt=Date of Death

6. ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA IN SECOND COMPLETE REMISSION IS ASSOCIATED WITH SIGNIFICANT LONG TERM SURVIVAL AND THE MODIFIED EBMT SCORE PREDICTS NON-RELAPSE MORTALITY IN THIS PATIENT GROUP

Frazer J,1 Couban S,2 Doucette S,3 Shivakumar S2

1Faculty of Medicine, Dalhousie University, Class of 2017, 2Division of Hematology, Department of Medicine, Dalhousie University and Queen Elizabeth II Health Sciences Centre and 3Research Methods Unit, Department of Community Health and Epidemiology, Queen Elizabeth II Health Sciences Centre

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with high morbidity and mortality, but can poten-tially cure carefully selected patients in second remission (CR2) of acute myeloid leukemia (AML). We sought to describe the post-transplant outcomes of a cohort of patients transplanted in Halifax to identify whether this is a worthwhile treatment for patients with relapsed AML,

validate prognostic risk groups derived by Michelis et al1 in this inde-pendent population, and determine which pre-transplant factors pre-dicted overall survival (OS), relapse, and non-relapse mortality (NRM) in this Atlantic Canadian cohort.

Methods: We conducted a retrospective chart review of 55 consecutive patients between 17 and 65 years of age who underwent allo-HSCT for AML CR2 from 1992-2013 in Halifax. Kaplan-Meier curves were used to assess outcomes in the three prognostic groups identified by Michelis et al1 and hazard ratios were used to describe the independent effects of pre-transplant variables on outcome.

Results: OS 1, 3, and 5 years post-transplant was 60%, 45.5%, and 37.5% respectively. Of the 36 patients who died after allo-HSCT, 19 patients (52.8%) died in relapse. Of these 19 patients, the time to relapse ranged from 1.5 to 22.5 months with a median of 5.6 months (IQR 3.2 – 13.0). Seventeen patients (47.2%) died from non-relapse related causes, including complications of graft versus host disease (GVHD). Seventeen patients (30.9%) were diagnosed with grade II-IV acute GVHD, 10 (18.2%) had grade I acute GVHD, and 28 (50.9%) did not have acute GVHD. Twelve patients (21.8%) were diagnosed with extensive chronic GVHD, 15 (27.3%) had limited chronic GVHD, and 28 (50.9%) did not have chronic GVHD. Our analysis did not reveal a statistically significant difference in OS (P = 0.85), relapse mortality (P = 0.92), and NRM (P = 0.46) between the three prognostic groups defined by Michelis et al.1 None of the pre-transplant variables exam-ined were significantly associated with increased OS, the only variable significantly associated with lower relapse rate was female sex (P = 0.04), and the only variable found to significantly impact non-relapse mortality was a mEBMT score of ≤3 (P = 0.049).

Conclusion: The 37.5% 5-year OS of this cohort suggests that allo-HSCT offers patients with AML CR2 a far better chance of long-term survival than other options and is therefore worthwhile to pursue in carefully selected and informed patients. The favorable, intermediate, and poor risk groups identified by Michelis et al1 did not significantly predict outcomes in our Atlantic Canadian population, but it is possible that our smaller sample size prevented a significant outcome here. A large national study including our data is underway to validate these prognostic categories. Our study validates the mEBMT score as a useful tool to predict NRM in this population.1 Michelis, F. V. et al. (2013). Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR. Bone Marrow Transplantation, 48(11), 1450-1455.


May 13-16, 2015

SCIENTIFIC PROGRAM


7. PREDICTORS OF OVERALL AND PROGRESSION FREE SURVIVAL AFTER RELAPSE FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION FOR HODGKIN LYMPHOMA

Dhamko H,1 Atenafu E,2 Al-Farsi K,1 Tsang R,3 Keating A,1 Crump M,1 and Kuruvilla J1

Division of Medical Oncology and Hematology1, Department of Biostatistics2, and Department of Radiation Oncology3, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

Background: Primary treatment of Hodgkin lymphoma (HL) has excel-lent outcomes, but relapse occurs in 10-20% of favourable and 30-40% of advanced disease patients. Autologous stem cell transplantation (ASCT) is second-line therapy, after failure of anthracycline-based che-motherapy. Unfortunately, up to 50% relapse after ASCT. Since optimal strategy for these patients is unknown, we sought to characterize prog-nostic factors post-ASCT relapse that could impact treatment choice.

Methods: We retrospectively reviewed 122 HL patients at Princess Margaret Cancer Centre in Toronto, transplanted December 1986 – July 2008 who relapsed or progressed after ASCT. Primary outcome was progression free survival (PFS) from relapse post ASCT by Kaplan-Meier method. Overall survival (OS) from relapse was also studied. Univariate analysis via log-rank test was done for age, sex, Ann Arbor stage, time to relapse post-ASCT, hemoglobin, LDH and ECOG score at relapse post ASCT. Cox proportional hazards model was used for multivariate analy-sis. Data was analyzed with SAS with 2-sided P value <0.05 considered statistically significant.

Results: Median age at diagnosis was 28 years (range 11-63) and median time to ASCT, 21 months (range 2-172). At diagnosis, 43% had stage I-II, 25% Stage IV and 30% bulky disease, 60% had B symptoms, and 30% primary refractory disease. Univariate analysis of continuous variables revealed older age at diagnosis and at relapse post ASCT, earlier relapse time and high LDH at relapse post ASCT were associated with inferior PFS (p<0.05). Earlier time to relapse post ASCT, low hemo-globin and higher ECOG score post ASCT relapse were associated with inferior OS (p<0.05). Age, time to relapse and LDH remained indepen-dent risks for PFS (p<0.05), while hemoglobin and time to relapse re-mained risks for OS after multivariate analysis (p<0.05). From this anal-ysis and previous publications, categorical risks for PFS were defined: age at diagnosis > 50, LDH >280 (upper normal limit), time to relapse < 6 months and OS risks: time to relapse < 6 months and hemoglobin < 100 at relapse. Median PFS for patients with zero, one and two risk factors was 10 (95% CI 7-11), 7 (95% CI 5-11) and 3 months (95% CI

1-6), respectively. Median OS with zero, one and two risks was 37 (95% CI 28-45), 28 (95% CI 13-39) and 18 months (95% CI 9-37). As shown in the figure, the prognostic groups had a statistically significant differ-ence in both PFS and OS (p<0.05).

Conclusion: HL patients who relapse or progress after ASCT can be stratified into prognostic groups. The group with poorest PFS had two of three risks: age > 50, high LDH at relapse and time to relapse < 6 months, whereas worst OS seen in relapse < 6 months and HgB < 100 at relapse. While factors such as stage at recurrence aid in deciding loco-regional therapy, patients with poor prognostic factors at relapse could be selected for novel treatment while those with favourable fea-tures managed more conservatively.

SCIENTIFIC PROGRAM



8. BENEFIT OF SCREENING LUMBAR PUNCTURE PRIOR TO ALLOGENEIC STEM CELLTRANSPLANT IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML)

Habib L,1 How J2

1Department of Internal Medicine, McGill University. 2Division of Hematology, Royal Victoria Hospital, McGill University Health Center

Objective and Rationale: The practice of screening patients with AML by lumbar puncture (LP) prior to allogeneic stem cell transplant is variable across institutions. While this may allow for earlier detection and management of disease in the central nervous system (CNS), rates of positive results are thought to be low with current chemotherapy regimens. The procedure is potentially harmful to patients, and avail-able data is conflicting as to whether screening is of value. Our aim is to assess the incidence of positive cerebrospinal fluid analysis at pre-trans-plant screening and determine whether screening affected outcomes post-transplant. We sought to identify risk factors that could predict which patients would benefit from screening and in whom it could be safely avoided.

Methods: We identified 85 patients (23-65 years old; 41% female) who underwent allogeneic stem cell transplant for AML between 2004-2014 at the McGill University Health Centre. We performed a retrospec-tive chart review to determine pre-transplant LP results as well as collect baseline demographic, disease-related, and transplant-related outcome information.

Results: Median follow up for the entire cohort was 2.92 years. Ten patients (11.76%) had CNS involvement at any point in their disease course. Seven cases (8.23%) were detected during initial work-up of their leukemia; two patients (2.35%) were identified with pre-transplant screening; one (1.17%) developed CNS relapse post transplant. Univari-ate analysis was performed for gender, age, WBC, LDH, cytogenetics, and myeloablative versus reduced intensity conditioning. Only WBC as a continuous variable (p=0.032) and LDH above normal limits (p=0.024) were significantly correlated with risk of CNS involvement. Both patients identified at pre-transplant screening had an elevated LDH at diagnosis. For the cohort, overall survival (OS) at 2 years post transplant was 51% (95% CI 39%-62%) and disease free survival (DFS) at 2 years was 48% (95% CI 36%-59%). No significant difference existed between those who had a negative pre-transplant screening LP and those for whom screening lumbar puncture data was not available (OS p=0.9961, DFS p=0.8354). Those patients with known CNS involvement had similar DFS to the other patients (p = 0.932). No grade 3-4 adverse events were associated with LP in our cohort.

Conclusion: Rates of positivity on pre-transplant screening LP were low. For patients with available data, no patient with a normal LDH at diagnosis went on to have a positive screen nor develop CNS involve-ment at any time. The availability of a negative screening LP did not predict for any difference in DFS or OS. Based on this data, we recom-mend LP at diagnosis for any transplant-eligible AML patient with an elevated LDH or WBC at diagnosis. Pre-transplant screening for patients not identified at diagnosis does not appear to have any added benefit.

9. A SCOPING REVIEW OF EVIDENCE FROM RCTS ADDRESSING BEST TRANSFUSION PRACTICES FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Christou G,1 Iyengar A,1 Shorr R,3 Tinmouth A,1,2,5 Sheppard D,1,2,3,5 Tay J,1,2,3,5 Bredeson C,1,3,5 Moher D,5 Allan D1,2,3,5

1 Division of Hematology, and 2Centre for Transfusion Research, University of Ottawa, Ottawa, ON, Canada; 3 Blood and Marrow Transplant Program, and 4 Medical Library Services, The Ottawa Hospital, Ottawa, ON, Canada. 5 Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada

Background: Integration of available evidence from RCTs into care of patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) remains challenging due to variations in patient character-istics and established protocols that guide local practices. Transfusion support during stem cell transplantation is a mainstay of supportive care, however, transfusion of blood products has been associated with immune modulation, risk of infection and transfusion reactions that can be life-threatening. In alloHCT, increased transfusion needs have been associated with worse clinical outcomes. The extent to which strategies aimed at reducing transfusion needs can improve clinical outcomes for patients undergoing alloHCT remains unclear.

Objective: Through a scoping systematic review of the literature, we aim to summarize and facilitate integration of the best available evi-dence into clinical transfusion practices for patients undergoing alloHCT.

Methods: A scoping review of all RCTs in alloHCT (June 2013) identi-fied 627 records which were sorted into 8 aspects of care, including studies of transfusion practices (20 records). After full review of these records, 11 full-length English language articles were identified and included in our review. Articles were classified as addressing red cell, platelet, or other transfusion needs.

Results: Of the 11 articles included for review, 6 were RCTs comparing various platelet transfusion strategies (1070 patients; some autoHCT or leukemia therapy) and their effects on transplant or treatment-related outcomes. A total of 5 RCTs (557 patients, all alloHCT) examined the


May 13-16, 2015

SCIENTIFIC PROGRAM


utility of recombinant erythropoietin in reducing red cell transfusion de-pendence. Of the 6 RCTs addressing platelet transfusions, 2 examined the impact of platelet age, 3 compared the effect of using different platelet counts as transfusion triggers and 1 examined the utility of using high dose platelet units. Although more restrictive platelet trans-fusion strategies were successful at reducing platelet consumption, only 1 of 5 studies reported increased bleeding which was associated with a “no prophylaxis” transfusion strategy. The number of studies reporting on infection (4), GVHD (3), engraftment rates (3), survival (2), and hos-pital length of stay (2) was variable and no differences were noted. In the 5 RCTs examining the role of recombinant erythropoietin in the early post-transplant period, 3 of 4 trials reporting average hemoglobin levels showed a significant increase and 4 of 5 studies demonstrated a signifi-cant reduction in red cell utilization. The number of studies reporting on infection (2), GVHD (3), engraftment rates (5), survival (3), and hospital length of stay (2) was variable and no differences were noted. Formal assessment of the impact on quality of life and economic analyses were not reported consistently.

Conclusion: Only eleven RCTs addressing transfusion practices in allo-geneic HCT have been published, addressing a small range of questions regarding best practices. Regarding red cell transfusion needs, although erythropoietin can predictably increase the average hemoglobin level and reduce red cell transfusions, its lack of impact on clinical outcomes combined with its high cost limits enthusiasm. Regarding optimal plate-let transfusion strategies, prophylactic transfusions using a trigger of <10x109/L may reduce bleeding. Additional RCTs are needed to refine best transfusion practices in alloHCT.

10. EVALUATION OF ZOSTER PROPHYLAXIS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION USING VALACYCLOVIR FOLLOWED BY VACCINATION

Jamani K, Daly A, Storek JDivision of Hematology and Hematologic Malignancies, University of Calgary & Alberta Blood and Marrow Transplant Program

Rationale: Varicella zoster virus (VZV) disease occurs frequently post allo-HCT. While cutaneous disease is often complicated by debilitating post-herpetic neuralgia (PHN), visceral or CNS disease can be fatal. Studies have demonstrated that VZV disease is reduced during prophy-laxis with acyclovir; however, patients frequently develop VZV disease after discontinuation of acyclovir. Recently, the varicella vaccine has been found to be safe and immunogenic post allo-HCT. The optimal

prophylactic strategy for VZV disease post allo-HCT has not been estab-lished. Here we present a retrospective single-centre study, comparing pre-2007 prophylaxis, which consisted of less than 2 years of post allo-HCT acyclovir, with post-2007 prophylaxis, which consisted of 2 years of valacyclovir prophylaxis followed by vaccination. In both strategies, acyclovir was applied longer in patients on prolonged immunosuppres-sive therapy.

Objective: To evaluate the hypothesis that the cohort treated with the pre-2007 strategy (old group) had a higher cumulative incidence of VZV disease and PHN compared to the cohort treated with the post-2007 strategy (new group).

Methodology: Charts of patients undergoing allo-HCT in Calgary between January 2004 and December 2010 were reviewed. VZV disease was defined as clinical zoster or visceral/CNS disease confirmed by im-munostain or PCR. PHN was defined as pain in the affected dermatome persisting more than 3 months after the onset of the rash. Cumulative incidence of VZV disease and PHN were compared using Fine-Gray re-gression, treating relapse, graft failure, second malignancy and death as competing risks.

Results: 441 patients underwent first allo-HCT in Calgary during the review period. 53 were excluded due to inadequate data. 83 were treated with the new strategy, 106 with an old strategy and 199 experi-enced a competing event while on prophylaxis. Old strategies included less than 2 years of prophylaxis. Some patients in this group received delayed VZV vaccination when practice guidelines changed. 34 patients (32%) in the old group and 20 (24%) in the new group developed VZV disease. 3 episodes of VZV disease (at a median of 61 days post allo-HCT) in the old group and 7 episodes (at a median of 464 days) in the new group were associated with failure of prophylaxis (most associated with medication noncompliance). The old strategy was associated with a trend towards a higher cumulative incidence of VZV disease (HR 1.33, 95% CI 0.78-2.30, p=0.29). When events associated with medication noncompliance were excluded, the old strategy led to a significantly higher cumulative incidence of VZV disease (HR 1.95, 95% CI 1.03-3.69, p=0.04). PHN occurred in 9 patients (26%) in the old group and 1 patient (5%) in the new group. There was a trend towards higher cumulative incidence of PHN in the old group (HR 7.6, 95% CI 0.94-61.0, p=0.057). PHN was not observed in patients who developed VZV disease post vaccination.

Conclusions: The new strategy was associated with a trend towards less VZV disease and less PHN. Late noncompliance with prophylaxis was a significant contributor to VZV disease in the new strategy group.

SCIENTIFIC PROGRAM



If medication compliance late post allo-HCT can be improved, the new strategy is superior.

11. OUTCOMES OF MATCHED RELATED AND UNRELATED BONE MARROW TRANSPLANTATION AFTER REDUCED-TOXICITY CONDITIONING FOR CHILDREN SUFFERING FROM CHRONIC GRANULOMATOUS DISEASE

Teira P, MD,1 Cros G, MD,2 Bittencourt H, MD,1 Cellot S, MD,1 Vachon M-F, MSN,1 Decaluwe H, MD,2 Duval M, MD,1 Haddad E, MD2 CHU Sainte Justine, Department of Pediatric Hematology-Oncology1, Department of Pediatric Immunology2, University of Montreal, Montreal, QC, Canada

Introduction: Chronic Granulomatous Disease (CGD) is a life threaten-ing immune deficiency related to a defect of oxidative burst in phago-cytes. Patients experience severe bacterial or fungal infections, associ-ated with chronic granulomatous inflammation of various organs. The only curative treatment is a Hematopoietic Stem Cell Transplantation (HSCT). However, the use of HSCT is restricted by the risks of transplant related mortality related to myeloablative conditioning regimen and donors other than a match sibling. In 2010, Sainte Justine hospital took part in an international initiative of HSCT for CGD, based on a Reduced Toxicity Conditioning (RTC) and a HLA matched donor, either related or unrelated. Seven children were included in this study, followed by 7 others transplanted after the completion of the study.

Methods: Data were retrospectively extracted from medical charts for 14 consecutive children transplanted for CGD from 2010 to 2014. Donors were a matched sibling (3/14), or a matched unrelated donor (11/14). The RTC consisted of Fludarabine (180mg/m2), targeted Bu-sulfan (55% to 75% of standard dose) and rabbit Antithymoglobulin (7.5mg/kg) or Alemtuzumab (0.5mg/kg). Graft versus host disease (GVHD) prophylaxis relied on Ciclosporin and Mycophenolate associ-ated with Prednisone for patients with colitis.

Results: The median age at HSCT was 15 years (1-20). Previous history of severe infections included abscesses located in adenopathy (9/14), skin (8/14), liver (7/14) or lungs (10/14), with pulmonary aspergillo-sis proven for 5 patients. Septicemia (4/14) and osteomyelitis (2/14) were also common. Inflammation mainly presented as Crohn like colitis (5/14) and chronic lung inflammation (6/14). Three patients had re-ceived granulocytes transfusions previously. No patient had active infec-tion or inflammation at the time of transplantation.

All 14 patients engrafted. Acute toxicities before day 100 were very limited without any case of veino-occlusive disease or severe infection.

Severe (grade 3-4) acute graft versus host disease (GVHD) and chronic extensive GVHD were not observed. Three patients experienced immune haemolytic anemia (3/14) and nephrotic syndrome (1/14).

The main complication was secondary graft failure for 3/14 patients occurring at 6 months. All 3 patients engrafted durably after a second HSCT. Including second grafts, post 6 months after HSCT, chimerism was higher than 90% in 13/14 patients and 66% in one patient. With a median follow-up of 43 months (7-60), all patients are alive, cured from CGD and free from immunosuppressive drugs.

Conclusion: HSCT with a RTC and a matched unrelated donor is safe and effective for children with severe forms of CGD. Acute and chronic GVHD are uncommon. Secondary graft rejection is the main complica-tion, but can be successfully cured by a second HSCT.

12. TO PARTNER WITH PATIENTS TO IMPROVE HEMATOPOIETIC CELL TRANSPLANT OUTCOME: IMPLEMENTATION OF A PATIENT PARTNERSHIP PROGRAM WITHIN THE STEM CELL TRANSPLANT UNIT

Grondin F, Inf. BSc, Séguin-Charbonneau N, BPharm, MSc, BCOP, Kudelka E, BSc, Roger C, Inf. BSc, Thibault Y, social worker, Tremblay N, Inf. MSc and Lachance S, MD, FRCPC, CSPQ Stem cell Transplant Program, Maisonneuve-Rosemont Hospital, Université de Montréal.

Introduction: While considering hematopoietic cell transplantation (HCT), patients and their family face several problems and obstacles that may impact on their outcome or interfere with their quality of life. The priorities may not always be the same between patients and the health care professionals surrounding them. To improve the quality and experience surrounding the transplant process, the HCT program of HMR was selected to participate in a pilot project aiming at including patients within a multidisciplinary team. The goal of this partnership program is to identify areas within the program needing improvement and to include patients in the decision-making process and in the de-velopment of tools addressing the issue identified.

Study goals: A multidisciplinary transplant team was established in-cluding patients (2) and health care professionals (6) (nurses, pharma-cist, social worker, clerk and physician). Regular meetings were organ-ised during 3 cycles of 4 months each, under the supervision of experts in patient management, collaboration and partnership from Université de Montréal. The goal of the meeting was first to identify the theme for the continuous improvement cycle in health care partnership and


May 13-16, 2015

SCIENTIFIC PROGRAM


the tools needed to resolve the problems identified. Discussion during these sessions highlighted the challenges associated with the diagnosis of a life threatening disease, the complexity of treatment and the stress imposed on patients and on their families (social, financial and emo-tional). The burden of the physical symptoms associated with transplant and its complications (graft-versus-host disease), the fear of relapse and the difficulty to manage the medication (mean of 30 pills per day) were among the concerns expressed by patients and felt to be inappropri-ately evaluated by the transplant team.

Results: According to the multidisciplinary team, three problems needed to be addressed:

1. The prioritization of symptoms and problems at the time of out patient clinic visit

2. The understanding and management of the medication

3. The transfer of information between the hospital and community pharmacy

To resolve the first issue, members of the team worked on the develop-ment and implementation of a health related questionnaire summariz-ing key symptoms in each system and asking patient to report symp-toms of concern and to establish a list of problems to prioritize and address at the time of medical visit.

To address issues associated with medication management, a written and a visual guide were developed imaging and summarizing the role of each medication, their side effects and optimal schedule. An on-line table to self manage the list of medication and the changes in dosing were proposed. This table was also used to ease the transfer from in hospital to community pharmacy. These tools are currently being imple-mented and tested in the out patient transplant clinic and their impact on patient care and health care professionals satisfaction are being evaluated.

Conclusions: It is possible to include patients in the decision making process within a multidisciplinary transplant team. Their input contrib-utes to better identify problems impacting their health and quality of life. Patient partnership promotes collaboration among members of the transplant team and improves their understanding of the process. It gives patients and team members the opportunity to actively contribute to health care improvement.

13. PROPHYLACTIC ANTIBIOTICS AIMING GUT DECONTAMINATION WORSEN ACUTE GRAFT-VERSUS-HOST DISEASE AND SURVIVAL FOLLOWING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Letendre C,1 Routy B,2 Mehraj V,3 Charbonneau Séguin N,1 Gagnon K,1 Lachance S1

1 Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, Québec, Canada. 2 Gustave Roussy Comprehensive Cancer Center; Paris, France. 3 Research Institute, McGill University Health Centre, Montreal, QC, Canada

Introduction: The impact of commensal bacteria collectively known as the microbiota has long been recognized as a pivotal factor in acute graft-versus-host disease (aGVHD) in mice [1, 2] and humans [3]. High-dose conditioning chemotherapy prior allogeneic hematopoietic cell transplantation (aHCT) disrupts the gut epithelial barrier allowing bac-terial by-products to translocate into the peripheral blood and modu-lates T cell response and pro-inflammatory cytokines. This observation led to an effort by transplant centres to eliminate bacterial colonization prior to transplantation to decrease the risk of gram-negative bacterial translocation [4,5]. Fluoroquinolone based antibioprophylaxis became standard of care to modulate gut flora and reduce gram-negative trans-location and sepsis [6]. In this study, we analyzed if patients’ gut decon-tamination prior to allogeneic stem cells infusion, affects the incidence of aGVHD and survival.

Method: We retrospective reviewed the chart of 306 patients mean age 47 that underwent aHCT at Maisonneuve-Rosemont hospital between January 2005 and December 2010. Cipro or moxifloxacin were started at initiation of the conditioning regimen for gut decontamination, but omitted in patients with fluoroquinolone or penicilline allergy. We com-pared aGVHD incidence, lymphocyte count at day+14 and overall sur-vival in patients receiving or not antibioprophylaxis pre-transplant.

Results: AML was the most common indication of HCT (29.4%). A total of 47% patients received antibiotic at the time of conditioning regimen. Ciprofloxacin, as compared to no antibiotic was associated to lower overall survival 5.2 years vs 6.7 years (p<0.003). The incidence of aGVHD and Glucksberg grade [7] of skin, liver and gastro-intestinal (GI) aGVHD were higher in patients pre-treated with antibiotic (p<0.05). However, the lymphocyte recovery count at day 14 did not correlate with the severity of GVHD.

Discussion: This retrospective study suggests that gut decontamina-tion with antibiotics lead to microbiota disequilibrium and increased

SCIENTIFIC PROGRAM



incidence and severity of aGVHD. It also demonstrated that antibio-prophylaxis adversely affects patient’s outcome. Multivariable analyses are required to rule out confounding factors. Without undermining the role of antibiotic prophylaxis to prevent infection in aHCT setting, treat-ment with broad-spectrum antibiotics have a detrimental impact on the commensal bacteria present in the gut. This imbalance could have con-tributed to the pathophysiology of GVHD and worsened prognosis, and should be explored further.

Conclusion: There is a tight relationship between GI tract microbiota disruption, mucosal injury, and alloreactivity leading to GVHD. Antibio-prophylaxis can disrupt the GI flora and impact on one of the causal factors of aGVHD. This ultimately highlights the importance of well de-signing future studies in order to adequately understand the impact of gut microbiota in HSCT.

References: 1. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia

after allogeneic stem cell transplantation. Heidegger, S., et al. Front Immunol. 2014, 5: p. 337.2. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell trans-

plantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Holler, E., et al.,Biol Blood Marrow Transplant. 2014, 20(5): p. 640-5.

3. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins. Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, Shimoda S, Iwasaki H, Shimono N, Ayabe T, Akashi K, Teshima T. Blood. 2012 Jul 5;120(1):223-31.

4. Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. van Bekkum, D.W., et al., J Natl Cancer Inst, 1974. 52(2): p. 401-4.

5. The microbiome and cancer. Schwabe, R.F. and C. Jobin, Nat Rev Cancer. 2013, 13(11): p. 800-12.

6. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations.Blennow O, Ljungman P, Sparrelid E, Mattsson J, Remberger M. Transpl Infect Dis. 2014 Feb;16(1):106-14.

7. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Glucksberg, H., et al. Transplantation, 1974. 18(4): p. 295-304.

14. EVALUATION AND SYSTEMATIC TREATMENT OF PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (GVHD) IN A SPECIALIZED MULTIDISCIPLINARY OUTPATIENT CLINIC: A 5-YEAR EXPERIENCE

Nair A, Nevill T, Toze C, Hogge D, Gerrie A, Song K, Abou Mourad Y, Sutherland H, Narayanan S, Power M, Nantel S, Barnett M, Forrest D and Broady RLeukemia/BMT Program of British Columbia, Vancouver General Hospital, BC Cancer Agency and the University of BC, Vancouver, BC, Canada

Background: Chronic GVHD (cGVHD) is a frequent and disabling complication of allogeneic SCT (alloSCT). A standardized, multidisci-plinary approach to this condition may optimize outcomes for affected patients (pts).

Methods: In 2008, the L/BMT Program of BC instituted a weekly cGVHD clinic designed to review patients with corticosteroid-depen-dent/refractory cGVHD to (a) develop an algorithmic approach to ongoing therapy to determine efficacy, (b) facilitate access to new/novel therapies, (c) provide referral to a designated network of subspecialists and (d) enroll individuals on clinical trials. A retrospective chart review was performed on the 112 new patients seen in this clinic between 06/2008 and 12/2012.

Results: There were 66 males and 46 females with median age 52 years (range 18-72). Pre-alloSCT diagnosis was AML (35 pts), lymphoma (20 pts), CLL (18 pts), CML (13 pts), ALL (10 pts), MDS (6 pts) or other (10 pts). The donor was matched related (62 pts), mismatched related (4 pts), matched unrelated (32 pts), mismatched unrelated (21 pts) or cord blood (3 pts). Excluding the latter, the vast majority of pts (98/109, 90%) had received mobilized blood stem cells. Conditioning was my-eloablative (76 pts), reduced-intensity (31 pts) or non-myeloablative (5 pts). Seventy-three pts (65%) had prior acute GVHD (aGVHD); 17 of these pts had required salvage therapies for steroid-refractory aGVHD [ATG (7 pts) and/or IL2r Ab (14 pts)]. Initial evaluation was a median of 25 months post-alloSCT (range 4-278). Most common sites of involve-ment were mouth (84 pts; 75%), eyes (79 pts, 71%), skin (79 pts, 71%) and liver (75 pts, 67%); other sites affected included GI tract (51 pts), lungs (28 pts), joints/fascia (22 pts) and genital tract (11 pts). Utilizing NIH consensus scoring/grading, 62 pts had severe, 44 pts moderate and 3 pts mild cGVHD (2 pts had late aGVHD and 1 pt no GVHD); most common sites given a score of 3 were liver (29 pts), skin (20 pts), GI tract (11 pts), eyes (8 pts) and lungs (7 pts). Treatments facilitated by the clinic included autologous serum eye drops (autodrops), special-ized eye lenses (lenses), extracorporeal photopheresis (ECP), Rituximab (Ritux), tyrosine kinase inhibitors (TKIs), mycophenolate mofetil (MMF), thoracoabdominal irradiation (TAI), monoclonal Abs (moAb), PUVA light therapy (PUVA) and Sirolimus (Siro). Responses were graded as partial (>50% objective response; PR), minor (subjective or <50% im-provement; MR) or no response/progression (NR). The best responses were seen in ocular cGVHD with autodrops (19/41 MR, 6/41 PR) and lenses (3/9 MR, 5/9 PR). Cutaneous and fascial GVHD responded mod-estly to ECP (4/26 MR, 8/26 PR), Ritux (8/21 MR, 2/21 PR) and TKIs (4/18 MR, 3/18 PR). Anecdotal responses were observed with MMF (4/11 MR+PR), TAI (1/5 PR), moAb (2/3 PR), Siro (1/2 MR) and PUVA (1/2 MR). As of February 1, 2015, 25 pts (22%) have died, 12 pts from complications of GVHD and 13 pts from relapse.

Conclusion: A multidisciplinary cGVHD clinic provides an important


May 13-16, 2015

SCIENTIFIC PROGRAM


service for alloSCT pts with a disabling complication, allowing for sys-tematic evaluation of novel therapies that can have significant efficacy.

15. DEFIBROTIDE TREATMENT FOR SEVERE HEPATIC VENO-OCCLUSIVE DISEASE: AN ANALYSIS OF CLINICAL BENEFIT AS DETERMINED BY NUMBER NEEDED TO TREAT (NNT) TO ACHIEVE COMPLETE RESPONSE AND IMPROVE SURVIVAL

Villa K,1 Richardson P,2 Kernan N,3 Grupp S,4 Martin P,5 Soiffer R,2 Martin R,6 Hannah A1

1Jazz Pharmaceuticals, Inc., Palo Alto, Inc., CA, USA; 2Dana-Farber Cancer Institute, Boston, MA, USA; 3Memorial Sloan Kettering Cancer Center, New York, NY, USA; 4The Children’s Hospital of Philadelphia, Philadelphia, PA; 5Duke University Medical Center, Durham, NC, USA; 6EUSA Pharma (an international division of Jazz Pharmaceuticals, plc), Oxford, UK

Objective: We calculated the number needed to treat (NNT) with de-fibrotide to achieve one complete response (CR) and to prevent one death 100 days post-hematopoietic stem cell transplantation (HSCT) in patients with severe veno-occlusive disease (sVOD), compared with historical controls (HC) who did not receive defibrotide, to evaluate how the NNT compares with NNTs of other efficacious treatments for acute, life-threatening conditions.

Rationale: Hepatic veno-occlusive disease, a potentially life threat-ening complication of HSCT, results from endothelial damage. sVOD, typically characterized by multi-organ failure, is associated with >80% mortality. Defibrotide is an oligonucleotide that stimulates restoration of thrombo-fibrinolytic balance and endothelial-cell protection. Data pre-sented are based on primary and secondary endpoints from a pivotal phase III trial that formed the basis for approval of defibrotide in the EU for treatment of sVOD following HSCT.

Methodology: A pivotal phase 3 study examined the efficacy and safety of defibrotide 25 mg/kg/day in patients with sVOD (n=102) com-pared with HC with sVOD (n=32). The primary endpoint was CR (im-provements in total bilirubin and resolution of multi-organ failure mea-sured by renal and/or pulmonary dysfunction) by day+100 post-HSCT; secondary endpoints included day+100 survival post-HSCT. NNT is the reciprocal of the absolute risk reduction (1/ARR), where ARR equals the control minus experimental event rates.

Results: Day+100 CR was achieved in 23.5% of defibrotide-treated patients and 9.4% of HC (P=0.013), yielding an NNT of 7 (1/(0.235-0.094)). Day+100 survival was 38.2% in the defibrotide group and 25.0% in the HC group (P=0.034). Therefore, the NNT to prevent one death was 8 (1/(0.382-0.25)). To compare this analysis with NNTs in

other studies, a literature search identified recent clinical trials in acute conditions with high short-term mortality; NNTs ranged from 1–59.

Conclusions: This pivotal phase 3 trial showed improved day+100 CR and survival in defibrotide-treated patients compared with HC not re-ceiving defibrotide for sVOD. The NNT to achieve this benefit proved either comparable to or lower than NNTs for other interventions in criti-cal care.

Support: Jazz Pharmaceuticals

16. OUTCOMES OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT) IN PATIENTS WITH MYELOFIBROSIS (MF) EXPOSED TO JAK1/2 INHIBITORS

Shanavas M,1 Popat U,2 Michaelis L,3 Fauble V,4 McLornan D,5 Klisovic R,6 Mascarenhas J,7 Tamari R,8 Arcasoy M,9 Mead A,10 Gergis U,11 Ukaegbu O,12 Kamble R,13 Storring J,14 Majhail N,15 Romee R,16 Lew J,7 Pagliuca A,5 Vasu S,6 Ernst B,4 Atenafu E,1 Hanif A,3 Champlin R,2 Hari P,3 Gupta V1

1Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 2Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3Haematologic Malignancies and Stem- cell Transplantation Program, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 4Mayo Clinic Cancer Center, Scottsdale, AZ, USA. 5King’s College Hospital NHS Foundation Trust, London, UK. 6The Ohio State University Wexner Medical Center, Columbus, OH, USA. 7Icahn School of Medicine at Mount Sinai, New York, NY, USA. 8Memorial Sloan Kettering Cancer Center, New York, NY, USA. 9Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA. 10Oxford University Hospitals NHS trust, Oxford, UK. 11Weill Cornell Medical College New York City, New York, USA. 12Vanderbilt University Medical Center, Nashville, Tennessee, USA. 13Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA. 14McGill University Health Centre, Montreal, QC, Canada. 15Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio, USA. 16Washington University School of Medicine, St. Louis, MO, USA

Background: JAK1/2 inhibitors (JAK#) have the potential to effectively control MF-related symptoms, and improve the clinical status prior to HCT. However, the clinical experience is limited, and data are conflict-ing. (Robin et al, Blood-2013/ASH abstract-306; Stübig et al, Leuke-mia-2014). Additionally, the relationship between the response to JAK #, and outcomes of HCT is not clear.

Patients and Method: In this multi-institutional retrospective study, we evaluated the outcomes of 93 MF patients (pts.) who had exposure to JAK# prior to HCT. A working definition of response to JAK# was es-tablished inspired by IWG-MRT criteria. (Table1). The primary end point was overall survival (OS) from the date of HCT.

Results: Median age at HCT was 59 years (range 32-72 years). Diag-nosis was primary-MF (n=53), post polycythemia-MF (n=20), or post essential thrombocythemia-MF (n=20). DIPSS-plus score at the time of HCT was low in 2 (2%), INT-1 in 19 (22%), INT-2 in 47 (52%), high-risk

SCIENTIFIC PROGRAM



in 22 (24%), and not available in 3 pts. Conditioning was full-intensity in 42 (45%), and reduced-intensity in 51 (55%). Donors were matched sibling in 36 (39%), matched unrelated in 47 (51%), and mismatched or haplo-identical in 10 (11%).

JAK# used were ruxolitinib (n=84), momelitinib (n=6), or others (n=3). Sixty-five (70%) pts used JAK# leading to HCT, and stopped 0-16 days prior to conditioning regimen; 23 (25%) pts had discontinued the medi-cation at least 4 weeks prior to HCT due to progression or intolerance, and in 5 pts this information was not available.

Among pts who used JAK# leading to HCT, “withdrawal symptoms” were reported in 10 (15%), and were more common in pts who stopped JAK inhibitors ≥ 6 days prior to conditioning regimen compared to those who stopped within 0-6 days (26% vs. 11%, p=0.06). Primary graft failure was reported in 3 pts (3%). The cumulative incidence of grade ≥2 acute GVHD at 100 days was 44%, and chronic GVHD at 2-years was 53%.

Medina follow-up of survivors were (2-53) months. During this period 12 (13%) pts had relapse/progression and 31 (33%) died. Probability of 2-year OS of whole cohort was 62% (95% CI, 50%-73%). Patient in group-A (n=22) had significantly superior survival p=0.01(Fig.1). In a limited multivariate analysis, response to JAK# was the strongest in-dependent factor for survival (p=0.004). DIPSS-plus high-risk category (p=0.04), and mismatched/haplo donor groups (p=0.04) were other independent factors for survival.

Conclusion: Our data suggest that use of JAK# prior to HCT does not have adverse effects on early transplant outcomes. The HCT outcomes in patients responding to JAK# are particularly encouraging.

1. Gp-A: Clinical improvement: ≥50% reduction in palpable spleen length for spleen palpable by ≥10 cm, or complete resolution of splenomegaly for spleen <10 cm)

2. Gp-B: Stable disease: spleen response not meeting the criteria of clinical improvement

3. Gp-C: New onset anemia requiring transfusions, or increase in blast to 10 -19%.

4. Gp-D: Progressive disease: Loss of spleen response or progression of splenomegaly or requiring splenectomy due to symptomatic splenomegaly

5. Gp-E: Progressive disease: Leukemic transformation (blast ≥20%)

Figure 1. Overall survival after HCT by response to pre-transplant JAK # therapy

17. IMPACT OF CIPROFLOXACIN PROPHYLAXIS ON ANTIMICROBIAL RESISTANCE IN NEUTROPENIC LEUKEMIA/STEM CELL TRANSPLANT PATIENTS

Warkentin D, PharmD,1 Mach A, Pharmacy student,2 Lacaria K, BSc Pharm,1 Roscoe D, MD,3 Lau T, PharmD,1 Bowie W, MD,4 and Broady R, MBChB5

1 UBC/Pharmaceutical Sciences, Vancouver General Hospital. 2 Pharmacy student, Faculty of Pharmaceutical Sciences, UBC. 3 UBC/Medicine, Faculty of Pathology and Laboratory Medicine, Vancouver General Hospital. 4 UBC/Medicine, Faculty of Medicine, Department of Infectious Diseases, Vancouver General Hospital. 5 UBC/Medicine, Faculty of Medicine, Leukemia/BMT Program of BC

Background: Fluoroquinolone (FQ) based antibacterial prophylaxis has been shown to reduce the frequency of neutropenic fevers and in-fection-related mortality in chemotherapy-related neutropenic patients. The prolonged use of FQ prophylaxis is however associated with the ap-pearance of resistant strains with the emergence of bacteria displaying cross-resistance to B-lactams and aminoglycosides. At our institution ciprofloxacin is administered to patients receiving consolidation che-motherapy in the outpatient unit. The emergence of a breakthrough infection of FQ resistant bacteremia is of particular concern in the group of patients.

Objective: At our institution we observed a significant increase in bacteremia due to FQ resistant E coli in the outpatient setting. This observation prompted us to evaluate the fecal flora to determine the influence of ciprofloxacin in the development of resistance to FQ during treatment.

Methodology: To evaluate induction of ciprofloxacin resistant isolates, perirectal swabs were collected at the following time points: pre-induc-tion, prior to each cycle of consolidation therapy, pre-HSCT and at the


May 13-16, 2015

SCIENTIFIC PROGRAM


end of therapy. Growth from the swabs were investigated for antibacte-rial resistance. In addition, we prospectively collected all episodes of infection from blood and urine and documented sensitivity patterns in these samples.

Results: Between May 2013 to August 2014, 86 patients with acute leukemia were enrolled at the Leukemia/Bone Marrow Transplant Program of BC. We report the findings of the first 66 patients. Median age of 61yrs (range; 21-74): 39/86 (45%) were female. The majority of patients received 7+3 induction chemotherapy followed by either HiDAC and or HSCT consolidation. Ciprofloxacin prophylaxis was ad-ministered for chemotherapy-induced neutropenia in almost all patients receiving consolidation chemotherapy. Seven patients received a FQ within 14 months of admission.

The majority of patients had perirectal swabs prior to each cycle of

chemotherapy. The median number of perirectal swabs collected per patient was 3.

The bacterial isolates were compared before and after each cycle of prophylaxis. Ciprofloxacin-resistant organisms were identified using perirectal swabs in 9 patients prior to prophylaxis and 7 patients after prophylaxis. E. coli was the most commonly identified organism. Mul-tiple courses of prophylaxis for sequential chemotherapy did not induce quinolone resistance. Interestingly, quinolone-resistant organisms were detected using swabs in 14% of all patients before the initiation of prophylaxis. Bacteremia with FQ-resistant organisms occurred in 9% of patients prior to prophylaxis and none during FQ prophylaxis. A variety of organisms were isolated during bacteremia. The FQ-resistant organ-ism identified in the perirectal swabs preceded a FQ-resistant bactere-mia in 2 patients.

Induction Consolidation HSCT

I II III

N 66 50 39 13 20

Febrile neutropenia 61/66(92%) 20/50(42%) 17/39(44%) 7/13(54%) 18/20(90%)

Bacteremia 24/66(36%) 3/50(6%) 7/39(18%) 2/13(15%) 3/20(15%)

Bacteruria 11/66(17%) 1/50(2%) 1/38(3%) 1/13(8%) 2/20(10%)

Cipro-resistant org 2/24(8%) 0 0 0 0

Positive perirectal swabs 10/65(15%) 8/42(19%) 3/28(11%) 2/13(15%) 3/17(18%)

Cipro-resistant org 9/10(90%) 7/8(88%) 3/3(100%) 2/2(100%) 2/3(67%)

Conclusions: Ciprofloxacin prophylaxis for neutropenia did not appear to result in a significant induction of FQ-resistant organisms. However, we detected colonization of ciprofloxacin-resistant organisms, predomi-

nantly E. coli, prior to prophylaxis. The colonization of ciprofloxacin-resistant E.coli may influence FQ prophylaxis in the future.

SCIENTIFIC PROGRAM



18. MODERATE/SEVERE GRADE OF CHRONIC GRAFT VERSUS HOST DISEASE AND YOUNGER AGE (LESS THAN 45 YEARS OLD) ARE RISK FACTORS FOR AVASCULAR NECROSIS IN ADULT PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Bhella S, MD, Uhm J, MD, Alam N, MBBS, Gupta V, MD, Kuruvilla J, MD, Lipton J, MD, PhD, Messner H, MD, PhD, Seftel M and Kim D Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada

Background: Avascular necrosis (AVN) is a debilitating complication of allogeneic hematopoietic cell transplantation (alloHCT).

Methods: A retrospective review of 845 consecutive patients ≥ 17 years of age who underwent alloHCT at Princess Margaret Cancer Centre from 2002 to 2013 was conducted to determine the incidence and risk factors for AVN. Univariate and multivariate analyses were conducted using EZR using cumulative incidence method considering competing risk.

Results: 48 cases of AVN were identified. Median follow up duration among survivors was 3.4 years. Frequent locations of AVN were: hip (n=37), shoulder (n=13), knee (n=13), ankle (n=2), wrist (n=1), and elbow (n=1).

Incidence of AVN was 6.3% (95% CI 4.6-8.5%) and 8.9% (6.5-11.8%) at 4 and 8 years respectively. Risk factor analysis revealed the following were significantly associated with higher risk of AVN in a univariate analysis: age < 45 (p=0.0039), grade 3-4 acute GVHD (vs grade 0-2; p=0.054), de-velopment of chronic GVHD(vs no chronic GVHD; p=0.000016), reduced intensity conditioning (vs myeloablative; p=0.017) and a diagnosis of acute leukemia (vs others; p=0.045). Multivariate analysis confirmed two risk factors: 1) younger age (≤45 years), 9.0% vs 4.4% (p=0.011, hazard ratio (HR) 2.134, 95% CI [1.186-3.843]) and 2) chronic GVHD develop-ment, 10.2% vs 1.4% (p=0.0002, HR 5.762, 95% CI [2.289-14.510]).

Incidence of AVN was 15.7% in patients with moderate to severe grade chronic GVHD and 3.6% in those with mild grade GVHD(p=0.00015).

A risk score model was generated assigning 1 score to each risk factor and summing the score thus dividing into three groups: low (score 0, n=349, 41.3%), intermediate (score 1, n=379, 44.9%) and high risk(score 2; n=116, 13.7%). This risk score could stratify the patients according to AVN risk (p=2.49x10-10). The risk of AVN was 1.5% (0.5-3.6%) in low, 6.2% (3.7-9.5%) in intermediate and 20.8% (13.0-29.9%) in high risk group.

Conclusions: Moderate/severe grade of chronic GVHD and younger age (≤45 years old) are key risk factors for AVN following allogeneic HCT.

Figure 1: Incidence of avascular necrosis according to the risk score based on the development of chronic GVHD and age (45 years old or younger)

19. FLAG-IDA AS FRONTLINE INDUCTION OR SALVAGE THERAPY FOR PATIENTS WITH HIGH RISK AND/OR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML)

Bhella S,1 Atenafu E,1 Schuh A,1 Minden M,1 Schimmer A,1 Gupta V,1 Seftel M,2 Alam N,1 Yee K1

1 Princess Margaret Cancer Centre, University of Toronto. 2 Department of Medical Oncology and Haematology, University of Manitoba, CancerCare Manitoba

Background: Therapy for patients (pts) with high risk and relapsed/refractory AML is unsatisfactory. Since January 2011, we have employed FLAG-IDA as first line therapy in pts with high risk AML (i.e. poor risk cytogenetics, antecedent MPN or MDS, or therapy-related AML), or as first salvage in pts with primary refractory/relapsed AML, in an attempt to improve CR rates, OS and to permit more pts to advance to allogeneic stem cell transplantation (alloSCT).

Methods: This retrospective review evaluates outcomes of pts with high risk and primary refractory/relapsed AML who were treated with FLAG-IDA between January 2011 to December 2014 at the Princess Margaret Cancer Centre.


May 13-16, 2015

SCIENTIFIC PROGRAM


Results: 46 pts received FLAG-IDA as first induction [median age 58.5 y (21-76 y)] and 69 pts as salvage [median age 51 y (18-76 y)]. Overall CR rates (CR + CRp) for frontline (n= 43 evaluable) and salvage therapies were 79.1% (88% CR; 11% CRp) and 57.9% (70% CR; 30% CRp), respectively; whereas, CR durations were 3 (0.5-15) mos and 6 (0-58) mos, respectively. CR2 duration for relapsed pts was 4 (1-12) mos. Pts who achieved a CR/CRp had an improved OS (log-rank test, p<0.0001). Pts who received frontline FLAG-IDA had an improved OS compared to those who received it as salvage (p=0.0116). Of the 28 (61%) pts who received frontline FLAG-IDA, achieved a CR/CRp and had a donor, 40% (n=11) underwent alloSCT. Of the 44 (64%) pts who received salvage FLAG-IDA, achieved a CR/CRp and had a donor, 50% proceeded to alloSCT. Median time to plts > 100 x 109/L in the frontline and salvage groups was 31 (20-148) days and 36 (17-136) days, re-spectively. Median time to ANC > 1 x 109/L in the frontline and salvage groups was 30 (14-85) and 33 (17-87) days, respectively. 48% and 62% of pts in the frontline and salvage groups had fungal infections. Median follow up time was 8 (1-64) mos. OS at 1 year in the frontline and salvage groups was 57.8% and 68.6%, respectively.

Conclusions: Toxicities associated with FLAG-IDA induction are ac-ceptable and are similar in untreated and pre-treated groups. FLAG-IDA induction can result in durable CR rates, permitting pts with either high risk or primary refractory or relapsed AML to proceed to alloSCT.

20. CLINICAL STUDIES OF EX VIVO EXPANSION OF HEMATOPOIETIC STEM CELLS TO ACCELERATE ENGRAFTMENT AFTER UMBILICAL CORD BLOOD TRANSPLANTATION: A SYSTEMATIC REVIEW

Damien P,1,2 McIntyre L,2,3 Fergusson D,2,3 Shorr R,4 Tinmouth A,1,2 and Allan D1,2

1 Hematology& Bone Marrow Transplant, The Ottawa Hospital. 2 The Ottawa Hospital Research Institute, Clinical Epidemiology Program. 3 Department of Medicine (Division of Critical Care), University of Ottawa. 4 Medical Library Services, The Ottawa Hospital

Background: Since the first human umbilical cord blood (UCB) trans-plant in 1988, UCB has emerged as an important source of hematopoi-etic stem cells (HSCs) for transplantation. Widespread public banking facilities ready access to many stored units. UCB requires less stringent HLA-matching compared with bone marrow or peripheral blood grafts and may be especially useful for patients without matched donors. A significant barrier to greater use of UCB is the limiting dose of HSCs that can be collected. Low absolute numbers of CD34+ cells in CBUs con-tributes to delayed or failed engraftment. A key strategy to overcome limiting HSC doses is ex vivo expansion of progenitors and increasing

numbers of published studies and ongoing trials of UCB expansion have been observed in recent years.

Objective: We sought to perform a comprehensive and contemporary review of ex vivo HSC expansion strategies that have been used in clini-cal studies to accelerate hematopoietic recovery after UCB transplan-tation. Synthesizing knowledge in this emerging field will allow us to identify the most promising strategies that would inform transplant centres, cord blood banks, blood establishments and international reg-istries in their efforts to maximize the utility of UCB transplantation.

Methods: Our search of published and ongoing clinical studies fo-cussed on patients (children and adults) undergoing UCB transplant with units that were treated ex vivo with the goal of expanding HSCs. Studies that did not specifically aim to expand HSCs cells were excluded (ie. expanding mesenchymal cells). Studies that addressed HSC expan-sion without transplantation were excluded. Outcomes captured in our analysis include the degree of HSC expansion, hematopoietic engraft-ment rates in transplant recipients, and post-transplant survival. Our systematic search was performed in MEDLINE, EMBASE, and Cochrane (September 1, 2014) and registered clinical trials were searched on clin-icaltrials.gov and the World Health Organization’s International Clinical Trials Registry Platform (September 1, 2014).

Results: After screening 3247 published records obtained in our systematic search, 22 clinical trials were included for further detailed review. Using standardized data extraction, we observed a chronologi-cal evolution of molecules used for HSC expansion. Before 2005, ex-pansion media included classical growth factors (SCF, TPO and/or EPO) whereas more recent studies have addressed smaller molecules, includ-ing copper chelators or nicotinamide which reflect the more recent discovery of HSC differentiation inhibitors. The creation of an evidence network that would allow indirect comparison of HSC expansion strate-gies is possible for different outcomes, including the degree of ex vivo HSC expansion and rates of engraftment following transplantation.

Conclusions: While interventions described to date appear safe and feasible, the small number of patients enrolled in published studies limits direct comparison to control groups and indirect comparisons between studies. The evolution of new expansion protocols is promis-ing. The resource intensity of ex vivo expansion strategies continues to limit broader applicability.

SCIENTIFIC PROGRAM



21. HOSPITALIZATIONS AMONG ADULT SURVIVORS OF CHILDHOOD CANCER TREATED WITH STEM-CELL TRANSPLANTATION

Ali M,1 Nathan P,1 Gassas A,1 Agha M,2 Greenberg M,1,2 Pole J,2 Schechter T1

1Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; 2Pediatric Oncology Group of Ontario, Toronto, Ontario, Canada.

Background: Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) has become standard components of therapy for several pediatric malignancies. As HSCT improves survival among those afflicted with these malignancies, and supportive care advances diminish the acute toxicities of HSCT, the risk for late complications in survivors is of increasing concern. We have recently shown that nearly 80% of patients survive beyond 2-years after HSCT. However, knowl-edge regarding the burden of morbidity after HSCT at an adult age is sparse. Frequency of hospitalizations can serve as a proxy measure of morbidity in this population.

Objectives: Our objective was to assess number of hospitalization epi-sodes in long-term adult survivors of childhood malignancies treated by HSCT in a tertiary centre.

Methods: We used record linkage between the SickKids’ clinical trans-plant database, the Canadian Province of Ontario’s pediatric cancer registry (POGONIS) and health care utilization data housed at the In-stitute for Clinical Evaluative Sciences (ICES). The study population was children diagnosed between 1986 and 2005, who were less than 18 years old at the time of the diagnosis and survived 5 or more years from diagnosis. Hospitalizations were captured from the later of each survi-vor’s 18th birthday or 5 years after HSCT until the end of the follow-up period (December 2011) or death.

Results: The cohort consisted of 242 long-term adult survivors who were followed for a mean of 12.3 years. Of these, 148 underwent al-logeneic and 86 autologous HSCT. Mean age at HSCT for the alloge-neic group was 11.5 years (SD: 4.7) and 11.0 years (SD: 5.3) for the autologous group. A total of 262 hospitalizations were documented in adults post allogeneic HSCT, representing a rate of 0.15 hospitalizations per follow-up year. Univariate analysis revealed that age >10 years at cancer diagnosis (RR=3.53, 95% CI: 2.34-5.33), age >10 years at HSCT (RR=5.88, 95% CI: 2.89-11.85), and female gender (RR=1.70, 95% CI: 1.33-2.18) were associated with an increased rate of hospitaliza-tion. The underlying diagnosis, ALL vs. AML was not associated with increased rate of hospitalization despite the use of total body irradiation

among ALL patients. A total of 106 hospitalizations were documented in adults post autologous HSCT, representing a rate of 0.09 hospitaliza-tions per follow-up year. Age >10 y-o at time of HSCT (RR=2.29, 95% CI: 1.29-4.04) and female gender (RR=1.70, 95% CI: 1.15-2.52) were associated with increased rate of hospitalization.

Conclusions: We have identified risk factors for hospitalization in adults who underwent HSCT during childhood. Future studies will focus on length of stay and the indications for these hospitalizations.

22. POST-THAW CD34 ENUMERATION: STABILITY OF SAMPLE BEFORE ANALYSIS

Simard C, Jobin C, Néron SResearch and Development, Héma-Québec, Quebec City, QC

Background: Post-thaw enumeration of CD34 in cord blood sample posed several specific challenges relative to fresh blood. One of them is the stability of the thawed sample and what is the available time window to proceed to analysis. To answer this specific question, we analyzed frozen cord blood sample immediately, 1h, 2h and 3h after thawing.

Methods: Frozen cord blood samples were thawed and diluted in Sa-line-Dextran-HSA. CD34 and CD45 cell counts and viability were mea-sured with BD Stem Cell Enumeration Kit. However, the lysis step was replaced by a dilution of the sample in PBS-BSA 1%. For each sample, enumerations were done immediately and 1h, 2h and 3h after dilution. The samples were kept at room temperature and protected for light.

Results: Viability, CD45 and CD34 enumeration gave similar results between 0h and 3h. No significant statistical differences were observed between conditions by ANOVA analysis.

Conclusion: For the post-thaw enumeration of CD34, samples are stable for up to three hours at room temperature once diluted in Saline-Dextran-HSA. This should provide more than enough time for sample staining, analysis, and redo the analysis if needed.

23. CORD BLOOD THAWING: COMPARISON OF ALTERNATIVE THAWING SOLUTIONS RELATIVE TO DEXTRAN BASED SOLUTION

Jobin C, Simard C, Néron SResearch and development, Héma-Québec, Quebec City, QC

Background: For cord blood graft, frozen units have to be thawed and diluted in a solution made of saline 0.9%, Dextran 10%, Human Serum Albumin (HSA) 5%. Although this solution works well, there’s actually a


May 13-16, 2015

SCIENTIFIC PROGRAM


shortage of injectable Dextran solution, making it increasingly difficult to use this thawing method. To address this important clinical issue, the purpose of this study was to evaluate alternative thawing solutions to replace the Dextran based one if needed.

Methods: Frozen cord blood samples were thawed and diluted in either Saline 0.9%, Plasmalyte A, Plasmalyte 148, Plasmalyte 148-Dextrose, Alburex 25 or Saline-Dextran-HSA as control. Additionally, Plasmalyte solutions were tested supplemented with HSA 5%. CD34 and CD45 cell counts and viability were measured with BD Stem Cell Enumeration Kit.

Results: The Plasmalyte-HSA 5% solutions and Alburex 25 gave CD34 recoveries similar to the Dextran based solution. Viability and yield were similar in all these solutions. Solutions without HSA gave significantly lower recovery and viability.

Conclusion: Alburex 25 and Plasmalyte solutions with HSA 5% could be potential substitutes for the Dextran based solution. Plasmalyte A with HSA 5% is a particularly interesting alternative since it’s already used for the thawing of peripheral blood units.

24. NUMERATION OF COLONY-FORMING UNIT GRANULOCYTE-MACROPHAGE (CFU-GM) COLONIES IN CORD BLOOD USING AN AUTOMATED INSTRUMENT: STEMVISIONTM

Elmoazzen H, Halpenny M, Martin L,Yang LCanadian Blood Services, Ottawa, Ontario

Background: Successful cord blood (CB) stem cell transplantation is associated with the quantity and potency of stem cells harvested in a cord blood unit (CBU). Building a successful cord blood bank (CBB) requires selection and banking of these high quality CBUs. To achieve this, CBBs focus on accurate, standardized testing methods to deter-mine CBUs with the highest quantity of hematopoietic progenitor cell populations. The colony forming unit (CFU) assay is the gold standard in vitro functional assay for measuring the number of progenitor cells in human hematopoietic cell samples. The Canadian Blood Services National Public Cord Blood Bank (NPCBB) initiated operations as of September 30, 2013. Herein, we describe our experience using the au-tomated STEMvision™ for imaging and scoring colonies in the CFU-GM assay.

Study Design and Methods: Traditionally, numeration of CFU-GM is performed manually based on morphological criteria with an inverted microscope. Accurate classification and counting of colonies can be challenging as manual counting of CFU assays is time consuming and

costly for cord blood banks that may perform large numbers of assays each day. Our experience and other reports have confirmed that colony counting is a major source of variation in the CFU-GM assay due to in-dividual interpretation of colonies and lack of standardized procedures. In order to standardize colony counting, minimize both inter-operator and inter-laboratory variations, we implemented STEMvision™ (Stem Cell Technologies) - an automated instrument and computerized system with sophisticated image analysis software for scoring CFU-GM colo-nies. Following manufacturer’s recommendation, SOPs were developed to perform CFU-GM assay on 412 eligible CBUs after volume reduction and prior to cryopreservation. Three plating concentrations of WBCs (0.4x105, 0.2X105 and 0.1x105) in duplicate plates were incubated at 37°C, humidified (>95%) incubator with 5% CO2. Cultures were scored on day 14 using STEMvisionTM.

Results: In addition to validation studies performed by manufacturer, prior to implementing the STEMvisionTM, an in house study was con-ducted at NPCBB. STEMvisionTM and manual counting (by an expe-rienced technician) was parallel performed to score CFU-GM colonies from samples obtained from CBUs to confirm correlation. During opera-tions at the NPCBB, the STEMvision™ has been to score colonies from CFU-GM assays that were performed on CBUs after volume reduction / pre cryopreservation. Our results demonstrated a mean CFU-GM of 21.5 x 105 (+/- 11.6) per unit.

Summary: 1) Validation studies demonstrate that the STEMvisionTM imaging and counting of CFU-GM has good correlation with the manual microscope counting. 2) The introduction of the automated imaging scoring system of STEMvision™ improves reproducibility and minimizes both inter-operator and inter-laboratory variations experienced with microscope determination. 3) Digital images can be stored in the com-puter for future review or further classification if required. 4) Our results (using STEMvisionTM) support implementation for high-throughput op-erations associated with cord blood banks. 5) NPCBB is positioned to performed data analysis using this CFU data set and future engraftment outcome measurement. In addition, other CBU quality data, such as TNC and CD34+ will be used in these future studies.

SCIENTIFIC PROGRAM



25. UMBILICAL CORD BLOOD PROCESSING: FIRST YEAR OPERATIONS AT THE CANADIAN BLOOD SERVICES, NATIONAL PUBLIC CORD BLOOD BANK

Elmoazzen H, Halpenny M, Martin L, Yang LCanadian Blood Services, Ottawa, Ontario

Background: Umbilical cord blood (UCB) stem cells have great medical potential and are currently being used as an alternative source of he-matopoietic progenitor cells for patients in need of transplantation. As the potential uses and the demand for genetically diverse UCB inven-tory continue to grow, there is a global tendency to encourage public cord blood banking. The Canadian Blood Services, National Public Cord Blood Bank (NPCBB) initiated operations as of September 30, 2013, for UCB collection, processing, testing, cryopreservation, storage and distribution. The purpose of this abstract is to report the results of UCB processed during first year operations at the NPCBB.

Study Design and Methods: Before initiating operations at the NPCBB, all collection, processing and testing methods completed an extensive validation process completed by the Canadian Blood Services Validation team with Quality Assurance Department final approval for operations. From September 30 of 2013 to September 29, 2014, UCB units were collected from 3 collection sites using a combination of both in utero and ex utero collection methods. A total of 412 UCB units were processed, cryopreserved and stored for transplantation purposes. All these units initially qualified as per an in-house developed quality acceptance criteria: collection volume >40ml, TNC (total nucleated cell counts) > 1.3x109 for ethnically diverse and >1.5x109 for Caucasian. All UCB units were processed within 48 hours of collection by appropri-ately trained NPCBB staff following established SOPs. Processing was completed using the SepaxTM 2 (Biosafe) Cord Blood Processing Unit - a fully automated, functionally closed and sterile system. The Bioar-chiveTM system (Cesca Therapeutics) was used for cryopreservation and storage. Each UCB unit was evaluated post processing / pre cryopreser-vation for TNC recovery, CD34+, viability and Colony Forming Units - Granulocyte Macrophage (CFU-GM). UCB units processed in the first 12 months of operations at the NPCBB were retrospectively reviewed.

Results: After volume reduction / pre cryopreservation the means of TNC, CD34+ cells, CFU-GM, and viability per unit were 1.37x109±0.40, 5.74X106±3.34, 21.54X105±11.60, and 96.51%±2.41, respectively. SepaxTM post processing mean TNC recovery of 78.91% was obtained.

Summary: Our results demonstrated: 1) NPCBB has designed, vali-dated and implemented a standardized, automated processing and

cryopreservation methodology enabling reproducible banking of high quality cord blood units. 2) Sepax 2 processing unit with cord blood specific software and single use processing kits is highly efficient and results in consistent cell recoveries. 3) UCB testing instrumentation has been successfully implemented at the NPCBB including the XE-2100 He-matology Analyzer (Sysmex) for TNC, FC500 Flow Cytometer (Beckman Coulter) for CD34+ / viability and STEMvision (Stem Cell Technologies) for CFU assay.

26. CYP2C19*17 GENETIC POLYMORPHISM – AN UNCOMMON CAUSE OF VORICONAZOLE TREATMENT FAILURE

Abidi M,1 D’Souza A,2 Kuppalli K,3 Ledeboer N,4 Hari P2

1Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. 2Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. 3Division of Infectious Diseases, Department of Medicine, Loyola University Medical Center, Maywood, IL. Division of Infectious Diseases, Department of Medicine, Hines Veterans Affairs, Hines, IL. 4Division of Microbiology, Medical College of Wisconsin, Milwaukee, WI.

Background: A 48 year old male, allogeneic hematopoietic stem cell transplant recipient with extensive graft versus host disease was ad-mitted with invasive pulmonary aspergillosis 6 months after transplant. Chest computerized tomography (CT) scan showed bilateral lung opaci-ties and he required intubation. Antimicrobials included intravenous cefepime, azithromycin and voriconazole 300 mg Q12h. Voriconazole infusion time was over 90 minutes. Bronchoalveolar lavage (BAL) fluid cultures grew 10,000 cfu/ml Pseudomonas aeruginosa and 1,000 cfu/ml Aspergillus fumigatus. Nucleic acid amplification testing was posi-tive for Mycoplasma pneumoniae. He received treatment with intrave-nous voriconazole for two weeks, and a serum voriconazole drug level was sent. He clinically improved, was extubated, and switched to oral voriconazole 300mg Q 12h. Four days after this transition had been made, his serum voriconazole level was reported as undetectable. Clini-cally his respiratory status worsened with chest CT showing worsening opacities bilaterally in upper and lower lobes. He was switched to IV voriconazole 400mg Q 12h and micafungin was added. Repeat serum voriconazole level was sent. A week later this result also returned unde-tectable despite high dose intravenous voriconazole therapy. Since the patient had been on intravenous voriconazole at both times that thera-peutic drug monitoring had been done this eliminated the possibility of undetectable voriconazole levels being secondary to poor oral absorp-tion of the drug. We suspected that he might be an ultra metabolizer of voriconazole.

Methods: Cytochrome assay was requested from an outside labora-


May 13-16, 2015

SCIENTIFIC PROGRAM


tory (LabCorp, Burlington NC). The methodology employed was DNA analysis of the cytochrome P450 2C19 gene including the alleles for poor metabolizers *1, *2, *3 *4, *5, *6, *7 and *8 as well as the ultra-metabolizer alleles *17. This was performed on the Tm Bioscience /Luminex Universal Array Platform using primer extension chemistry. Multiplex PCR amplifies DNA fragments containing mutations associ-ated with the alleles mentioned above. Primer extension then gener-ates a biotin-labeled product that hybridizes to complementary, bead-immbolized probes to permit flow-sorted detection of noth bormal and mutation sequences.

One week after the addition of Micafungin he showed clinical and ra-diological improvement. CYP2C19 genotype testing was positive for the *17 translocation indicating he was an ultra metabolizer for voricon-azole. He was discharged home on micafungin with plans to switch to liposomal amphotericin B if there was any worsening.

Results: Genetic polymorphism of CYP2C19 modulates enzyme activity and significantly different plasma concentrations are observed despite identical dosing schedules. Studies reveal polymorphisms to contrib-ute to pharmacokinetic variability. Individuals may be categorized as ultra rapid metabolizers (UM) (CYP2C19*1/*17 CYP2C19 *17/ *17); extensive metabolizers (EM) (CYP2C19*1/*1); intermediate metabolizer (IM) (CYP2C19*1/*2 and CYP2C19*1/*3) and poor metabolizers (PM) (CYP2c19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). This study high-lighted that voriconazole is influenced by CYP2C19 polymorphism and gene based adjusted dosing is important to achieve therapeutic drug levels.

Conclusions: Our case highlights voriconazole therapy failure and the importance of therapeutic drug level monitoring. While non-adherence and enzyme induction could certainly be factors affecting voriconazole levels, CYP2C19 polymorphisms should also be considered in patients with very low voriconazole concentrations for treatment of invasive fungal infections.

27. PUBLIC AND FAMILY CORD BLOOD BANKING: A GOOD QUALITY SAMPLE IS A GOOD QUALITY SAMPLE

Casbourn L,1,2 Niapour M,2 Gallagher L,1 Virro J,2 Semple E1,2

1 Cells for Life, Markham, ON, 2 Victoria Angel Registry of Hope Public Cord Blood Bank, Markham, ON.

When using cord blood for transplantation, the choice of the sample is influenced by factors such as HLA match and available cell dose/kg bodyweight but also by the reputation of the bank providing the unit

including accreditation status and previous transplant success.

In Canada both family and public cord blood banks are required to meet standards and guidelines set forth by CSA and Health Canada. In addi-tion, most family and public banks have voluntarily been accredited by AABB and/or FACT. This demonstrates commitment to quality and gives an additional level of confidence that the bank is working according to current quality standards.

The concept of public banking is to store samples that have been donated for the use of anyone in need, whereas family banks are guardians of the sample for the family’s use. Public banks are servic-ing the current use of cord blood, i.e. transplantation for hematologi-cal diseases, and are only storing samples with the highest cell counts to maximize the available patient population. Typically approximately 20% of collected samples are stored. Family banks are storing for use in traditional transplantation but also for future applications in areas such as regenerative medicine. Most collected samples are stored in the family bank setting as 1) samples with a lower cell count is adequate for a small patient, 2) a small sample can be used in double transplants and 3) a small cell dose may be adequate for use in regenerative medi-cine. When using a sample from a public bank, the transplant physician relies on the health assessment of the donor and infant that was done at the time of donation. Some public banks contacts the donor before release to get a status on the child (i.e. no genetic or hematological disease) but this can sometimes be difficult. When using a sample from a family bank, the current family history can be evaluated and the use of a sample that would be unsafe can be avoided.

Other differences between public and family banking include: availabil-ity of the programs (limited geographically vs country-wide), program funding (government/charity funding vs fee for service), cost for the health care system of acquiring a sample for transplantation ($40,000 vs $0).

The rate of release of samples from Canadian family banks is approxi-mately 1/5000 samples stored. About 60% of these samples have been used for treatment of hematological diseases, mostly for siblings, and 40% have been used in clinical trials for Type I Diabetes and Hypoxic brain injuries.

In conclusion, public and family banks are serving different purposes and should both be available for expecting families to make an informed choice if they want to donate or save the cord blood. As standards and regulatory requirements are the same for both types of banks, trans-plant physician should feel confident that the sample is safe and of

SCIENTIFIC PROGRAM



good quality whether it comes from an accredited family or public bank.

28. ICING ORAL MUCOSITIS: ORAL CRYOTHERAPY IN MULTIPLE MYELOMA PATIENTS UNDERGOING AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT

Chen J,1 Rajakumar I,1 Seabrook J,2 Fulford A3

1Department of Pharmacy Services, London Health Sciences Centre (LHSC), 2

Department of Paediatrics, LHSC, 3 Department of Hematology/Oncology, LHSC.

Background: Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high dose mel-phalan conditioning chemotherapy. This has significant impact on the patients’ quality of life during their transplant process. Oral cryotherapy, defined as chewing of ice chips, has been documented to be potentially effective in reducing oral mucositis from some chemotherapy agents, including melphalan. The aim of this study was to examine the effec-tiveness of the cryotherapy protocol implemented within the autologous hematopoietic stem cell transplant program at LHSC in 2010.

Methods: A retrospective chart review was conducted of adult mul-tiple myeloma patients who received high dose melphalan condition-ing therapy for autologous hematopoietic stem cell transplant. Patients were identified through the hematopoietic stem cell transplant data-base from the department of hematology/ oncology. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints in-cluded duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition (TPN) use.

Results: One hundred and forty patients were included in the study, 70 patients in the pre-cryotherapy group (2006-2009) and 70 patients in the post-cryotherapy group (2010-2013). Both oral mucositis incidence and severity were found to be significantly lower in the post-cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy, compared to 67 (95.7%) in the pre-cryotherapy group [p < 0.001]. The severity of oral mucositis experienced was assessed using of the WHO oral toxic-ity scale from grade 0-4. The mean oral mucositis severity experienced in the pre-group was 2.24 (±1.1) vs. 1.76 (±1.4) in the post-group [p = 0.03]. Two of the secondary endpoints, oral mucositis duration and use of parenteral narcotics, were also significantly reduced in the post-cryotherapy group. Duration of hospital stay and use of TPN were similar between the two groups.

Conclusion: The oral cryotherapy protocol at LHSC resulted in a sig-nificantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inex-

pensive and generally well tolerated practice, in patients receiving high dose melphalan for autologous hematopoietic stem cell transplant.

29. SECURING INFORMED CONSENT AT STEM CELL DRIVES: A UBC STEM CELL CLUB IMPLEMENTATION OF WORLD MARROW DONOR ASSOCIATION GUIDELINES

Fingrut W,1,2 Parmar S1

1 UBC Stem Cell Club, BC, Canada. 2 Department of Medicine, University of British Columbia, BC, Canada

Securing informed consent at time of donor registration to a stem cell donor-database is an important moral, ethical, and legal obligation. Moreover, two studies by Switzer et al. (2003, 2004) found that donors who felt less informed at various points in the donor recruitment, evalu-ation, and workup process were more ambivalent about donation and less likely to proceed with the donation process if asked. In 2003, the World Marrow Donor Association (WMDA) published a set of sug-gested procedures for securing informed consent of potential stem cell donors. However, implementation of these guidelines at stem cell drives remains unclear.

Stem cell drives run by the UBC Stem Cell Club include five stations: prescreening, informed consent, registration, swabbing, and reconcili-ation. Here, we describe the UBC Stem Cell Club’s approach to imple-ment WMDA’s informed consent guidelines at our drives. At the pre-screening station, potential donors learn about the principles of stem cell donation, including the match process, diseases treated by stem cell transplant, nonremuneration of donation, and the possibility of do-nation to any donor worldwide. They are also informed about donor eligibility requirements, including health restrictions. At the informed consent station, registrants are handed an information brochure, shown diagrams illustrating donation procedures, and educated about poten-tial risks of donation, donor/patient anonymity, and the right to with-draw. Both stem cell and bone marrow transplantation procedures and risks are discussed. At the registration station, registrants sign a consent form, and learn about the process for data collection, storage, usage, and confidentiality. At the swabbing station, the registrant is asked three questions to confirm they understand the material covered in the informed consent station:

“What happens if you are a match?”, “What are the risks involved in do-nating stem cells?”, and “What happens if you say no?”. Finally, at rec-onciliation, registrants are asked if they have any additional questions, and they are instructed of their responsibility to update their health/


May 13-16, 2015

SCIENTIFIC PROGRAM


contact information as applicable. Registrants are told that OneMatch will attempt to trace potential donors if they are found to be a match and cannot be contacted.

In summary, this presentation outlines the UBC Stem Cell Club’s ap-proach to implementing the WMDA informed consent guidelines at each station of our stem cell drives. Our group’s strategy for securing in-formed consent at drives aims to lessen the ambivalence of the donors we recruit, and can be easily adopted by any individuals or groups that organize stem cell drives.

30. REDIRECTING INELIGIBLE AND NON-OPTIMAL STEM CELL DONORS TO HELP IN OTHER WAYS

Fingrut W1,2

1Department of Medicine, University of British Columbia. 2UBC Stem Cell Club

Canadians can register as unrelated stem cell donors either online or at a stem cell drive, where they provide consent and a tissue sample (buccal–swab) for Human Leukocyte Antigen (HLA) allele typing. Eli-gible donors are ages 17-35; are in general good health; are willing to donate to anyone in need; and are covered by provincial healthcare insurance.

The most-needed donors are young and ethnically-diverse males, who are informed and committed. Patients are more likely to match to a donor in their own ethnic group, and there is therefore a need for Canada’s donor-database to reflect the ethnic diversity of Canada. Younger donors are associated with improved recipient survival, and male donors are associated with reduced transplant complications for the recipient. However, males under age 35 only represent ~12% of the current Canadian donor-database (~5% non-Caucasian males). Re-cruitment efforts should be focussed to register donors from these most-needed demographic groups, while ineligible and non-optimal donors should be redirected to help in other ways.

In this presentation, I propose and outline strategies and evidence-based key messages to redirect ineligible and non-optimal donor groups. The presentation equips Canadian Blood Services staff, community partners, and volunteers with instructions on what to say to donors who may not be a good fit for the unrelated donor registry. It contributes to the discussion about how ineligible or non-optimal stem cell donors can be most appropriately redirected to best help patients in need.

Proposed Strategies and Key Messages:

Ineligible or Non-optimal Donor Groups

Proposed Strategies and Key Messages

Donors older than 35 · “As people age, their stem cells age too”

· “Studies have shown that patients have a better chance of surviving when the donor is younger”

Females · “Studies have shown that when the donor is male, the patient has less chance of complications”

· “Today, three out of four stem cell donors chosen to help save a life are male”

· Encourage women to donate umbilical cord stem cells from baby if they plan to have a child

Individuals who lack provincial healthcare coverage (i.e. international students)

· Encourage them to sign up on their home country’s registry

Donors who are not in good general health

· “Donors need to be healthy, not just to protect the patient but also to protect themselves”

· Volunteers can refer to the website wiki.wmda.info for disease-specific in-formation regarding medical suitability

Donors who are unwilling to donate to anyone in need

· Explain that they would not know who they are donating too

Key messages which apply to everyone

· Encourage their family and friends who are males ages 17-35 to register

· Ask them to sign up for blood dona-tion by calling 1888-TODONATE

· Invite them to volunteer at and help promote stem cell drives

SCIENTIFIC PROGRAM



31. PATIENT’S PERSPECTIVE AND SATISFACTION WITH EMOTIONAL SUPPORT: WHAT DO PATIENT’S WANT?

Georgiou G,1 Ho E 2

1 Hematology/Hematopoietic Stem Cell Transplant Program, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences. 2Performance & Improvement, Hamilton Health Sciences

Introduction: Cancer imposes emotional, social, psychological, func-tional and spiritual consequences that are just as difficult for patients as the physical ones. All patients will experience some level of emotional distress throughout their journey, hence psychosocial support is an in-tegral component of cancer care. Good emotional support is dependent on the relationship built between the patient and care provider and their level of involvement, commitment, and concern about the patient (Attree 2001). Although emotional care is valued by patients and health care providers alike, many hospitals fall short in meeting patient’s psy-chosocial needs (Adamson et al, 2012). The Hematology/HSCT unit at the Juravinski Hospital and Cancer Centre uses a holistic approach to care which includes psychosocial support along the cancer continuum. Data obtained from the NRC Canada Patient Experience survey indi-cated that emotional support was scored less positively by patients, compared to other aspects of their care and experience.

Thesis: In order to better meet patient’s psychosocial needs, the hema-tology/HSCT Unit sought to gain insight into the emotional care needs of their patients and the specific behaviors that convey emotional support.

Summary:

Model Development: A qualitative approach using semi-structured patient interviews was used to collect data. The inclusion criteria in-cluded a length of stay of at least five days, the patient must be feeling healthy enough to participate in the interview, and must be fluent in English. Patients were asked four standardized, open-ended questions which explored staff behaviors, services provided by the unit, types of interactions with the team, and open suggestions about how to improve emotional support. Twenty patients were interviewed from November to December 2013. The interviews were recorded, transcribed, coded using key words, and the key words were categorized into dimensions. Four emotional support dimensions emerged from patient responses: Supportive Approach, Trust in Care, Communication and Resources. A model of emotional support was developed based on these dimensions.

Model Validation: The emotional support dimensions were reviewed by four clinical experts to achieve face validity. To test the construct validity of the model, a survey was developed consisting of questions

that were derived from the preliminary model. Two additional questions regarding overall ratings of care and emotional support were included. Thirty five patients were recruited to complete the survey from Decem-ber 2014 – February 2015 using the same inclusion criteria. The survey results were analyzed using the Pearson Correlation Coefficient and Reliability Alpha. Sixteen items in the model were found to have a sig-nificant positive correlation with the overall rating of emotional support. Eighteen items were found to have significant positive correlation with the overall rating of care. The reliability coefficient alpha was greater than 0.8 (p<0.05) for three dimensions in the model.

Conclusion: The patient’s perspective on what constitutes excellent care is increasingly being recognized as an integral aspect of quality improvement work. The voices of hematology/HSCT patients were used to develop a model of emotional support which will help to bridge dif-ferences in expectations between caregivers and patients and to guide efforts to improve care.

32. DEVELOPMENT OF A STANDARDIZED FOLLOW UP FOR PEDIATRIC TRANSPLANT LONG TERM SURVIVORS BY FAMILY PHYSICIANS

Friedrichi C, BSN, Richer J, BSN, Vachon M-F, MSN, Bittencourt H, MD, Teira P, MD, Duval M, MD, Cellot S, MDCHU Sainte Justine, Montréal, QC, Canada.

Indications for stem cell transplantation (SCT) in pediatric population are increasing and patients are expected to live long and productive lives. However, they do require lifelong follow up, dictated by the initial diagnosis and late toxicities. Like most pediatric centres, patients over 21 years old can no longer be followed by our pediatric team and need to be transfered to an adult facility. At our institution, we are facing the challenge of a lack of available resource to transfer all of our patients to an adult transplant facility. In this situation, how can we best provide patients with a proper and safe follow-up when the adult transplant centre cannot accept the entire patient cohort?

In order to achieve this goal, we have developed a standardized protocol to direct our patients toward the most appropriate facility. Referral to the adult transplant team is restricted to those patients presenting GVHD, he-matologic toxicity or more than two organs involvement. All of our other patients, which represent the vast majority, will be referred to their family physician with specific guidelines. However, most of them don’t have a family physician as the follow up of SCT patients may seem complex.

First, our protocol will help guide and support our patients in identify-ing a family physician which can take up to two years. Once a referring


May 13-16, 2015

SCIENTIFIC PROGRAM


doctor is found, the transplant physician and the nurse navigator will prepare a file containing the patient medical summary and guidelines detailing the recommended follow up and possible long term sequelea. Also, our team remains available to answer questions. Finally, we en-courage family physician to send us periodical summary charts.

Information about the recommended follow up and good life habits are previously given to patients to promote their autonomy and facilitate a smooth transition. This procedure is an important part of our teenag-ers transplant clinic that was just implemented. This procedure started about a year ago and so far, it seems to be a positive experience for everyone involved.

33. PRE-PROCESSING STORAGE TEMPERATURE EFFECTS ON THE POTENCY OF CORD BLOOD STEM CELLS

Letarte C,1,3 Rhéaume M-E,1,3 Fournier D,2 Chevrier M-C,2 Bazin R1,3

1,2Héma-Québec, 1Innovation R&D, Québec and 2Cord Blood Bank, Montréal; 3Laval University, Québec

Background: Umbilical cord blood (UCB) has been proven to be an important alternative source of hematopoietic stem cells (HSCs) mostly for pediatric patients suffering from hematologic disorders. Because of its many advantages over other sources of HSCs, such as ease of collec-tion, less stringent HLA restrictions and lower risks of developing GVHD, the use of UCB has expanded in recent years and led to a growing number of public cord blood banks (CBB) that operate under guidelines established by the regulatory organisms such as Netcord FACT, AABB or FDA. Despite the standardization of CBB procedures, some parameters remain unregulated, such as the pre-processing storage temperature. At Héma-Québec Public CBB, the units are kept at room temperature (RT) before being processed and cryopreserved within 48 hours after collection. Recently, a study using a mouse model of engraftment re-vealed that a pre-processing storage of 72 hours at room temperature might have deleterious effects on the HSC reconstitution capacity. This study also revealed that the HSC in vitro characteristics (viability, differ-entiation capacity) could not predict this loss of function. The aim of our study was to evaluate the impact of pre-processing storage temperature on HSCs, using the banking procedure in place in our public CBB.

Methods: Upon reception, cord blood units (CBUs) are split into two smaller units and stored at 4°C or RT until reaching 48 hours after col-lection before processing and freezing. The viability (flow cytometry), ALDH expression, proliferation and differentiation capacity (CFU) and in vivo hematopoietic reconstitution of Nod/SCID gamma null (NSG) mice

(n= 6-7 mice per group) are evaluated after thawing the stored units.

Results: Results obtained so far show that hematopoietic reconstitu-tion potential measured in NSG mice differed for each of CBUs tested, although the number of HSC (CD34+) injected (1.5 x 104) was similar in each experiment, suggesting that the long-term repopulating cell (CD34+CD49f+CD90+CD45RA-CD38-) content differs between each CBU. Importantly, there was no clear impact of the pre-processing tem-perature (4°C vs RT) on the viability of HSC, CFU and reconstitution potential of the CBUs tested. Moreover, our results showed that, in con-trast to the previously published study, the in vivo reconstitution could be predicted by CFU assays, since the best reconstitution was observed in mice grafted with cells from CBUs that yielded the highest number of CFU. Experiments to determine whether ALDH expression could be used as a marker for HSC reconstitution capacity instead of CFU or NSG reconstitution assays are underway.

Conclusion: Our ongoing experiments with additional groups of grafted NSG mice will help define the optimal conditions for UCB pro-cessing and banking and will permit to confirm the predictive value of CFU assays or of ALDH expression analysis for engraftment.

34. TNC BUT NOT CD34+ CELL RECOVERY IN BUFFY COATS IS INFLUENCED BY THE WAITING TIME BEFORE CORD BLOOD UNIT PROCESSING

Rouleau P,1 Rhéaume M-E,1,3 Fournier D,2 Chevrier M-C,2 Bazin R1,3 1,2Héma-Québec, 1Innovation, R&D, Québec and 2Cord Blood Bank, Montréal; 3Laval University, Québec

Background: The Héma-Québec Public Cord Blood Bank operates under guidelines established by regulatory agencies. The procedure for banking requires that each umbilical cord blood (UCB) unit is stored frozen within 48h of collection. Recently, we showed that the total nucleated cell (TNC) recovery in buffy coats (BC) prepared by volume reduction of whole UCB greatly varied between units processed shortly after collection compared to units processed at later times. Since the TNC count is an important criterion for clinical use of banked units, the present study was undertaken to better characterize the differential recovery of TNC in BC as a function of time after collection.

Methods: Cord blood units (CBUs) were stored at RT for defined periods of time before processing by centrifugation at 3500g for 10 min at RT and volume reduction to 21 +/- 2 ml using the Optipress. Group 1 consisted of CBUs (n=9) processed within 9h of collection (mean of 6.3h) and Group 2 contained CBUs (n=10) processed from 10 up to 48h (mean of 29h) after collection. The flow cytometry ISHAGE protocol

SCIENTIFIC PROGRAM



was used to establish TNC (CD45), stem cell (CD34), T cell (CD3), B cell (CD19) and granulocyte (CD15) counts as well as viability (7-AAD) in all BC and discarded red blood cell (RBC) fractions.

Results: In Group 1, TNC recovery in the BC fractions was 70.1 ± 4.0%. Virtually all stem cells and T cells (>99%) initially present in the CBUs, 87.0 ± 8.9% of B cells and 51.9 ± 7.8% of granulocytes were found in the BC fractions respectively, while the remainder of B cells and granu-locytes were found in discarded RBC fractions. In Group 2, TNC recovery in the BC fractions was, as expected from our previous study, much higher (91.1 ± 6.5 %; P < 0.0001). Once again, virtually all stem cells (>97%) and T cells (>96%) initially present in the CBUs were recovered in the BC fractions, together with 87.5 ± 9.7% of B cells and 80.5 ± 9.2% of granulocytes. In Group 2, the RBC fractions contained 12.5 ± 9.7% and 19.5 ± 9.2% of B cells and granulocytes respectively.

Conclusion: The difference in TNC recovery between BC fractions of CBUs from Group 1 and Group 2 is explained by the differential dis-tribution of granulocytes in the BC and discarded RBC fractions. The post-reduction recovery of stem cells and T cells (and to a lesser extent, of B cells) in BC fractions was excellent for CBUs from both groups and was not influenced by the duration of the hold period before process-ing. Since stem cells are of outmost importance for the current clinical applications, research and selection of CBUs should give priority to this parameter rather than TNC count.

35. DEFINING CATCHMENT AREAS FOR THE ORGANIZATION OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ONTARIO

Wang J,1 Hertz S,1 Bredeson C,2 Kuruvilla J,3 Matthews J,4 Xenocostas A,5 Herst J,6 Kaizer L,1 Kouroukis C1,7

1Cancer Care Ontario, 2The Ottawa Hospital, 3Princess Margaret Cancer Centre, 4Kingston General Hospital, 5London Health Science Centre, 6Health Sciences North, 7Hamilton Health Sciences Centre

Background: Cancer Care Ontario (CCO) is the provincial agency re-sponsible for the planning of adult cancer services. Since 2010, this has included hematopoietic stem cell transplantation (HSCT) in Ontario. To effectively plan for equitable access to services, CCO needs to under-stand where patients from different parts of the province access services at each of the six transplant centres. Consistent referral patterns can result in more predictable patient flow, allow the centres to more ac-curately project volumes and plan resources accordingly, and provide clear guidance to referring physicians to support timely referrals and access to services.

Approach: CCO collaborated with the clinicians and administrators at transplant centres to define catchment areas and recommend refer-ral patterns using the Local Health Integration Networks (LHINs) geo-graphical areas as a framework, while allowing for patient choice and traditional provincial travel patterns. The goals were to promote the delivery of HSCT as close to home as possible and to clarify roles of providers and hospitals in both referring and receiving patients for al-logeneic unrelated and related (ALLO-U and ALLO-R) and autologous (AUTO) transplant. A before/after analysis of provincial patient volumes was conducted to demonstrate the effect of implementing these catch-ment areas. The catchment areas were implemented in fiscal year 2012-2013, and referral patterns were analyzed from fiscal years 2010-2011 and 2011-2012 for the pre-implementation cohort (total volumes over 2 years - AUTO: 777, ALLO-R: 160, ALLO-U: 180) and fiscal year 2013-2014 for the post-implementation cohort (total volumes - AUTO: 505, ALLO-R: 78, ALLO-U: 120).

Results: For auto transplants, there was a reduction in the median percentage of patients that were treated outside of the recommended catchment areas, from 11% to 5% (p = 0.05). For ALLO-R, there was no change in the median percentage at 10%. For ALLO-U, there was an increase in the median percentage from 3% to 10% (p = 0.25). In some regions, the change was remarkable. As an example, prior to the implementation of catchment areas, 51% of AUTO patients who resided in the North East (NE) LHIN received their transplants in Sudbury, which means that about half of those patients had to travel outside of their LHIN to receive HSCT care. Following the implementation of the catch-ment areas, 88% of NE patients received their care in Sudbury. Overall, the median percentage fell from 7% to 6%; however, there was insuf-ficient data to show a statistically significant effect in the median per-centage across all types of transplant.

Conclusions: While there is variability in conforming to the catchment areas among the LHINs post-implementation, these results show that for some types of HSCTs, having defined catchment areas leads to more predictable and consistent referral patterns and patient flow.


May 13-16, 2015

SCIENTIFIC PROGRAM


36. FORECASTING THE DEMAND FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ONTARIO

Wang J,1 Hertz S,1 Bredeson C,2 Schuh A,3 Kuruvilla J,3 Kaizer L,1 Kouroukis C1,4

1Cancer Care Ontario, 2The Ottawa Hospital, 3Princess Margaret Cancer Centre, 4Hamilton Health Sciences Centre

Background: Cancer Care Ontario (CCO) is the provincial agency responsible for the planning of adult cancer services. Since 2010, this has included hematopoietic stem cell transplantation (HSCT) in Ontario. To effectively plan HSCT services, CCO needs to understand how many patients may be eligible and potentially benefit from this treatment.

Approach: An incidence-based forecasting model was developed to estimate and forecast the demand for HSCT services in Ontario. A step-wise approach was taken to: 1) identify clinical indications for HSCT; 2) develop incidence estimates and forecasts for each of the disease indications for HSCT; 3) develop and apply clinical algorithms to estimate the proportion of the incidence for each indication that could be eligible for HSCT. Data was taken from the Ontario Cancer Registry, Ontario Stem Cell Transplant Database, Ontario Ministry of Finance, and published literature. Expert opinion and consensus further informed decision making.

Results: The model was run and compared with historical data. In 2010, 541 patients received HSCT. Based on the model, we estimated that there were 640 to 746 patients in the province that could have been eligible for a transplant. Therefore, there may have been 99 to 205 patients who did not receive HSCT and may have potentially benefitted. However, in 2013, 703 patients received HSCT. The demand model had estimated that 669 to 780 patients would have been eligible for a transplant. This shows that in 2013 the capacity for HSCT appeared closer in meeting the demand for HSCT in Ontario. A regression on historical data guided by clinical judgment and demand estimates was used to forecast future HSCT volumes until 2017, where the projected demand for HSCT is between 704 to 822.

Conclusion: The demand estimates were used to understand capacity for HSCT services in Ontario and help plan for potential gaps in service. This methodology can be tailored and applied across other jurisdictions to assist with the planning of HSCT services. We predict an increasing demand for HSCT services in the future.

37. IN VITRO PRODUCTION OF MEGAKARYOCYTE PROGENITORS FROM NON-QUALIFIED CORD BLOOD UNITS FOR CLINICAL APPLICATIONS

Dumont N,1 Laganière J1 1Héma-Québec, Québec city

Background: Cord blood hematopoietic stem cells (CB-HSCs) offer the possibility of developing a myriad of in vitro-derived cellular products for a wide range of clinical applications. Since not all cord blood units received at Hema-Québec are suitable for banking, it would be ideal to exploit this source of stem cells further through the development of alternative products to those currently offered.

Thrombocytopenia is a frequent chemotherapy-induced side effect. Since platelet half-life is rather short, patients consequently require multiple transfusions to maintain acceptable levels for the prevention of hemorrhage.

The transfusion of megakaryocyte (MK) progenitors derived from CB-HSCs is expected to provide an interesting alternative to repeated platelet transfusions as it has the potential of increasing the amounts of platelets in patients up to a safe level and sustain such level for an extended period of time, in addition to being produced in a highly-controlled laboratory environment.

Methods: CD34+ HSC were purified using positive selection (EasySep Human Cord Blood CD34 Positive Selection Kit #18096) and were dif-ferentiated in vitro in a xeno-free culture medium (Stem span ACF, Stem cell technologies) containing TPO, SCF, IL-6 and IL-9 using a proprietary method of expansion at 39 celcius degrees for 6 to 14 days. Expanded cells were characterized for their expression of megakaryocytic markers and their colony-forming potential was assessed with megacult assays (StemCell Technologies #04971). MKs were also infused in NSG mice, orbital sinus blood was collected and platelet counts were performed by flow cytometry (BD Accuri C6 and FCS Express 4 Flow for data analysis) at various time points.

Results: With the method developed, we obtained MKs at a purity of over 80% in xeno-free conditions. We show that the MKs produced are functional in vivo , as infusion in immunodeficient mice lead to the production of a sustained amount of human platelets detectable within 5 days.

Conclusion: The procedure and culture conditions developed for the production of megakaryocytes from cord blood are completely exempt of animal-derived components. This high-quality cellular product com-

SCIENTIFIC PROGRAM



bined with the positive pre-clinical data shown here are promising for translation to the clinic.

38. USE OF STATINS TO AUGMENT PROGENITOR CELL FUNCTION IN PRE-CLINICAL AND CLINICAL STUDIES OF REGENERATIVE THERAPY AND IMMUNE MODULATION: A SYSTEMATIC REVIEW

Park A,1 Ranasinghe I,1 Pilon S,1 Sy R,2,4 Fergusson D,2 Allan D1,3

1 Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Canada 2 Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Canada 3 Divisions of Hematology, University of Ottawa, Ottawa, Canada 4 Gastroenterology, University of Ottawa, Ottawa, Canada

Background: Regenerative cell-based therapy is an emerging field with increasing promise. Mesenchymal stromal cells (MSCs) and vas-cular endothelial-like progenitor cells (EPCs) are two principal classes of progenitor cells used in cell-based regenerative therapy. Both MSCs and EPCs secrete paracrine factors that coordinate the overall repair response. HMG CoA reductase inhibitors (statins) can activate pathways to block apoptosis of MSCs and EPCs, prolonging cell survival and vi-ability and may improve their capacity to repair organ function follow-ing injury. The clinical potential of statin drugs for this indication of cell-based regenerative therapy remains ill-defined.

Objective: We sought to summarize the results of preclinical and clinical studies in a systematic review, to identify whether statins can improve organ recovery following tissue injury through the improved functioning of cells used in regenerative therapy.

Methods: A systematic search of the literature was performed in ac-cordance with PRISMA guidelines. A search strategy was developed to identify studies in MEDLINE, EMBASE, and PUBMED databases (1947 to June 25, 2013). Controlled clinical studies and controlled pre-clinical studies were included if they described the use of statin therapy or the administration of cells treated with a statin ex vivo, regardless of outcome, and reported on patient groups or animals with organ injury, tumor growth or immune disorders.

Results: Our systematic search yielded 771 records. Following a screen for relevance, a total of 100 records were identified and underwent more detailed eligibility screening. In total, 38 studies were included in the review: 7 were clinical studies involving human subjects and 31 were pre-clinical studies involving animal models. None of the clini-cal studies involved the administration of MSCs or EPCs but, instead, involved the administration of statins or placebo to patients and de-scribed the change in number and/or function of MSCs or EPCs which was correlated with recovery of organ-specific measurement outcomes.

Three main organ systems were addressed in the clinical studies, in-cluding cardiac (5 studies), vascular (1 study) and neurologic (1 study) systems. All 7 clinical studies reported benefit with statin therapy. A total of 18 pre-clinical studies used statin therapy ex vivo to treat MSCs or EPCs as part of cell-based transplantation therapy to repair cardiac (7 studies), vascular (5 studies), neurologic (5 studies) or orthopedic injury (1 study). All of these interventional cell-based pre-clinical studies reported benefit with statin therapy. In addition, there were 13 pre-clinical studies that involved the administration of a statin drug to the animal with subsequent measurement of MSC or EPC number and/or function which was correlated with the repair of various organ systems, including cardiac (2 studies), vascular (6 studies), neurologic (2 studies) and immunologic systems (3 studies). All of these studies reported benefit with statin therapy.

Conclusion: Our systematic review provides a foundation of encourag-ing results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs and EPCs. Our system-atic search highlights significant potential publication bias, however, and enthusiasm should be tempered when considering these positive results.

39. FUNCTIONAL IMPAIRMENT OF CD8+ T LYMPHOCYTES IN PEDIATRIC RECIPIENTS OF BONE MARROW OR UMBILICAL CORD BLOOD TRANSPLANTATION DURING THE EARLY POST-TRANSPLANT PERIOD

Fourati I,1,2 Gravel C,1,2 Caty M,1 Mezziani S,4,5 Le Campion A,1 Duval M,3,4,5 Soudeyns H1,2,3,5

1Centre de recherche du CHU Sainte-Justine; 2Department of Microbiology, Infectiology & Immunology, Faculty of Medicine, Université de Montréal; 3Department of Pediatrics, Faculty of Medicine, Université de Montréal; 4Hemato-oncology Service, CHU Sainte-Justine; 5Groupe de recherche en transplantation et immunologie du sang de cordon (GRETISC), Centre de cancérologie Charles-Bruneau, Montreal, Quebec, Canada.

Background: Umbilical cord blood transplantation (UCBT) is com-monly used to treat a variety of hematologic or neoplastic disorders in children. Compared to bone marrow transplantation (BMT), UCBT is associated with slow engraftment and a higher incidence of graft failure and opportunistic infections. During chronic viral infection and cancer, CD8+ T cells undergo functional and phenotypic changes that characterize a state of differentiation termed clonal exhaustion. We previously performed a detailed analysis of PD-1, CD244, BTLA, LAG-3, CTLA-4, and TIM-3 on peripheral CD8+ T cells in pediatric UCBT and BMT recipients. Results showed a transient increase in the frequency of CD8+ T cells that expressed either PD-1, CD244, BTLA, or LAG-3, or


May 13-16, 2015

SCIENTIFIC PROGRAM


co-expressing PD-1 and CD244 or PD-1 and BTLA during the first 100 days following UCBT. The aim of this study was to: a) further investigate if inhibitory receptor expression on CD8+ T cells is a marker of T cell ex-haustion rather than secondary to T cell activation; b) ascertain whether expression of exhaustion biomarkers by CD8+ T cells during the early post-transplant period leads to functional impairment.

Methods: Pediatric patients who underwent UCBT (n=8) or BMT (n=4) for the treatment of leukemia or other hematologic disorders were enrolled at CHU Sainte-Justine. Expression of CD69, CD45RA, CD27, CCR7, and exhaustion markers was measured ex vivo using multipara-metric flow cytometry. Intracellular cytokine staining was used to quan-titate production of IFN-γ and IL-2 in response to stimulation with PMA and ionomycin.

Results: Preliminary results showed low levels of expression of CD69, an early T cell activation marker, at the surface of CD8+ T cells ex-pressing exhaustion markers, suggesting that these cells were unlikely to be undergoing activation. Moreover, frequencies of cells PD-1, 2B4, BTLA and, LAG-3 were highest in effector memory T cells, suggesting that the differentiation of CD8+ T cells along the naïve-effector-mem-ory pathway is skewed during the first 100 days post-transplantation. Finally, cells co-expressing PD-1 and BTLA exhibited severely reduced production of IFN-γ and IL-2.

Conclusion: These results indicate that expression of exhaustion markers by CD8+ T cells in UCBT and BMT recipients correlates with functional impairment, providing a potential explanation for the inability of these cells to control opportunistic infections. This supports our previous find-ings that expression of at least one exhaustion marker by CD8+ T cells led to reduced proliferative activity following in vitro stimulation.

40. FACILITATING CORD BLOOD RESEARCH IN CANADA

Golder M,1 Mastronardi C,1 Allan D,2,3 Elmoazzen H,2 and Chargé S1

1Centre for Innovation, Canadian Blood Services, Ottawa Ontario. 2National Public Cord Blood Bank, Canadian Blood Services, Ottawa Ontario. 3Ottawa Hospital Research Institute, Ottawa Ontario

Introduction: Umbilical cord blood is a rich source of hematopoietic stem cells and has many applications both clinically and in research. Research performed with cord blood ranges from studies to improve cord blood collection, manufacturing, and storage processes; to studies evaluating the use of cord blood in the treatment of hematopoietic and non-hematopoietic diseases. A survey of Canadian researchers in 2010 found that access to cord blood for research was not adequate to meet

the demand and that the cord blood available for research was not always ethically sourced.

Design: In 2013, Canadian Blood Services launched the National Public Cord Blood Bank (NPCBB), which collects, processes, tests, and stores cord blood units for transplantation; however, not all collected cord blood is suitable for storage and transplantation. The Cord Blood for Research Program (CBRP) and NPCBB developed processes to distribute de-identified cord blood units not suitable for storage and transplanta-tion to the scientific community for biomedical research purposes, mini-mizing the number of cord blood units discarded and facilitating access to cord blood for research.

Results and Conclusions: In August 2014, the CBRP launched in Ottawa. Mothers donating to the NPCBB at The Ottawa Hospital are now given the option to donate to the CBRP if their baby’s cord blood is not suitable for storage and transplantation. The consent rate for research for mothers donating to the NPCBB has increased from 33% to 65% in the first 6 months of CBRP operations. Canadian researchers nationally are able to apply to receive cord blood products for research and, in the first 6 months of CBRP operations, 40 cord blood units have been distributed to 6 researchers from British Columbia and Ontario, to projects ranging from cord blood expansion to the hematopoietic reconstitution enhancing activity of osteoblasts. To further facilitate access to research cord blood samples for TOH and Ottawa Hospital Research Institute researchers, Canadian Blood Services and TOH have created a joint research working group that facilitates access to cord blood and related research samples that cannot be obtained through the CBRP due to study requirements.

41. ONEMATCH 2013 RETROSPECTIVE DONOR SELECTION STUDY: HLA MATCH LEVEL, REGISTRY AUTONOMY, AND CORD BLOOD USAGE

Greco-Stewart V, Killeen D, Haun S, and Mercer DCanadian Blood Services, OneMatch Stem Cell and Marrow Network, Ottawa

Objective: To review the options for hematopoetic stem cell (HSC) sources for each OneMatch patient involved in workup with an unre-lated donor or cord blood unit (CBU) in 2013 to address whether or not the most histocompatible donor was selected, whether OneMatch registrants were investigated/chosen where appropriate, and whether CBUs were selected preferentially over donors.

Rationale: HLA match level between donor/recipient pairs is consid-ered to be a significant indicator of post-transplant outcome. Cana-

SCIENTIFIC PROGRAM



dian Transplant Centres (CTCs) typically strive to match patients at the allele level of HLA-A, -B, -C, -DRB1, and -DQB1 loci to achieve 10/10 HLA match level. While OneMatch Search Analysts provide HSC search strategy and advice, donor selection is ultimately the responsibility of the CTC. Since high match levels are associated with the best post-transplant outcomes, review of patient searches was performed to ensure that optimal HLA-matched donors were selected. Autonomy in HSC sources is a hallmark of high-performing registries, thus utilization of OneMatch donors, where appropriate, was also examined. In 2014, Canadian Blood Services launched the National Public Cord Bank, so it was also imperative to examine CBU utilization by our CTCs.

Methodology: Alternate HSC prospects available to OneMatch pa-tients in workup were reviewed with respect to match level, registry of HSC origin, and product choice. To determine donor suitability, HLA match level was considered with secondary emphasis on donor age and gender.

Results: In total, 341 unique workups were examined. Of 302 workups involving donors, 218 (72%) were matched at 10/10 HLA genes and 84 (18%) were matched at 9/10. OneMatch donors were used in 25% and 6% of these instances, respectively. In 48% of cases involving 10/10-matched international donors, there were no suitable Canadian donors available, and in half of these instances there were no high-

probability 10/10 matches. Female donors comprised 5% Canadian donor workups, whereas 25% of international donors were female. There were 39 workups involving CBUs comprised of 20 pediatric and 11 adult patients. Only 4 (20%) of the pediatric cases did not involve in-vestigation of adult donors, and in these cases the prospects for 10/10 matched donors were poor or absent. For adult patients, donors were almost invariably investigated before CBU options were pursued. Non-Caucasian patients comprised 40% of pediatric and 45% of adult CBU investigations, respectively. Optimal HLA-matched HSCs were chosen consistently, although preference of mismatched Class I loci was vari-able. Mismatch at DRB1 was largely avoided for both donors and CBUs.

Conclusions: Optimal HLA-matched HSCs were chosen for OneMatch patients in accordance with established histocompatibility practices in 2013. OneMatch registry autonomy is limited by size and underrepre-sentation ethnic minorities; in almost half of instances in which inter-national donors were selected there were simply no OneMatch donors of comparable HLA match level. Female OneMatch donors were largely overlooked despite age and parity, and donors with the least ambigu-ous typing were preferentially selected. CBUs are rarely investigated as a primary source of HSC, even among pediatric patients.


May 13-16, 2015

SCIENTIFIC PROGRAM


Le Centre Sheraton Montreal Hotel Floor Plans

Niveau / Level 3 Niveau / Level A

Niveau / Level 4

SCIENTIFIC PROGRAM



About CBMTGThe Canadian Blood and Marrow Transplant Group (CBMTG) is a national, voluntary, and multi-disciplinary organization providing leadership and promoting excellence in patient care, research, and education in the field of BMT.

CBMTG’s vision is that Canada will be the best place in the world to have a blood and marrow transplant. Furthermore, the mission of the association is that the Canadian Blood and Marrow Transplant Group is the voice of experts working in the field of blood and marrow transplant.

The CBMTG’s values are: excellence, innovation, integrity, collaboration and professionalism in care, education and research in blood and marrow transplant. While the association’s philosophy is: CBMTG believes that every patient has a right of equal access to the highest quality of life saving care that can be provided by blood and marrow transplant professionals in Canada.

Based on this, our strategic priorities are as follows:

Education

Providing high quality educational programs that advance the practice of blood and marrow transplantation in Canada.

Research

Establish and organize an effective and sustainable research infrastructure for translational and clinical research.

Outreach

Increase the visibility and influence of CBMTG among members and the public.

Financial Capacity

To support, education, research and outreach initiatives through fundraising, partnerships and the establishment of a charitable organization.

CBMTG Membership:The CBMTG membership is made up of national and international physicians, nurses, laboratory technicians, pharmacists, and coordinators working in blood and marrow transplant.

FOR MORE INFORMATION, PLEASE VISIT WWW.CBMTG.ORG

may 13–16, 2015 · le centre sheraton hotel, 1201 boulevard rené–lévesque west, montreal, qc...

Documents