Prof M A Khan FCPS, FRCP.

Professor of BMT

BMT unit, Dept of Hematology

DMCH

Bone Marrow Transplantation in Bangladesh: our experience

CONFLICT OF INTEREST

I have no conflict of interest to declare.

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TOP STORIES

• Importance of bone marrow transplant

• Background history of BMT at DMCH

• Stem cell Transplant activity of Bangladesh

• Overall status of ASCT

• Complications of Autologous stem cell transplant

• Future goal

• Achievement

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WHY BONE MARROW TRANSPLANT IS NECESSARY ?

• 50 year male, banker suddenlydeveloped bodyache andweakness.

• Pathological fracture in femur.

• Dx: Multiple Myeloma IgGk, IIIB.

• Post chemo in remission.

• What is next?

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BMS

SPEP

WHY TRANSPLANT ?

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Michel Attal, NEJM , April 2017, vol. 376 no. 14

Outcome RVD

(chemo )

ASCT P value

Patient No 350 350

CR+ VGPR 48+29

=77%

59+29

=88%

0.02

MRD neg 65 % 79% <0.001

CASE HISTORY

• 18 Y boy, DLBCL, IIIB> CHOPx6 >relapsed after 1 yr.

• 28 Y male of HodgkinsLymphoma, IIIB, Rx : ABVD x6> end of therapy PET scanwas still positive for significantactive disease> Refractory HL.

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What should be next approach?

TRANSPLANT VS CHEMO IN RELAPSED LYMPHOMA

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5 Y EFS 46% in Transplanted

Vs

12 % in chemo alone.

Autologous Stem cell transplant is the standard ofcare in relapsed chemosensitive NHL as well as rHD.

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PRINCIPLE OF BMT

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Core steps :

1. Pre-transplant eligibility( age, PF, Disease)

2. Take the disease in remission

3. Mobilization of stem cell

4. Stem cell processing

5. Conditioning chemo( big dose!)

6. Stem cell infusion back

7. Post transplant care (in isolated Hepa

room, barrier nursing)

Now stem cells are

collected from blood

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10FATHER OF BONE MARROW TRANSPLANT

(Left )Edward Donnall Thomas (1920-2012) , the noble laureate in 1990 for

Stem cell transplantation.

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11ANCIENT BONE MARROW TRANSPLANT

First BMT Team of Dr Thomas

INDICATION OF STEM CELL TRANSPLANT

Autologous SCT: own stem cell

Allogeneic SCT: healthy matched donor’s stem cell

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1. Multiple Myeloma

2. Relapsed/refractory chemo sensitive Lymphoma

3. AML ( no matched donor)

4. Germ cell tumor

1. AML

2. ALL

3. MDS

4. Severe Aplastic Anaemia

5. Thalassemia major , Eß

DREAM OF BMT STARTED ON 2007 WITH MAKING INTERNATIONAL COLLABORATION

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2007 Saudi Team visited DMCH Prof Mamen Chandy, Prof Najmul

Ahsan, Prof Khan, Prof Deen Md. 2010: Prof Taher Pakistan

•2011 : Prof Khan to Vietnam

As a speaker on ‘BMT in emerging

countries ‘

•Project proposal rejected many

times.

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BMT

Prof M.A. Khan

Prof RuhulHaque

[Ex Health Minister]

Dr B. R.Dey

(MGH)

Policy

makingFinance

Infra

structure

HR develop

•Key persons meeting on 2011

•MOU signed bet’n DMCH & MGH

Key steps

INFRASTRUCTURE DEVELOPMENT

2012: site visit by MGH team 2012: work monitoring

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DMCH – 2 building BMT Unit at top floor

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Nurses Training Lab training

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Prof Ruhul Haq’s Visit

Decoration time

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Inauguration on 2013

WHAT’S MISSING?

Stem cell lab

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Third Party Inspection

HISTORY BEGINS HERE !

First ASCT on 10th March 2014 Press meeting

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36 ASCT by BMT Team >80 Stem cell apheresis

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TRANSPLANT ACTIVITY AT DMCH BY YEAR

0

1

2

3

4

5

6

7

8

9

65

0 01

12

3

6

1

1 1

2

2

1

10

2

0

1

AML

HD

NHL

MM

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0

10

20

30

40

50

60

70

1986

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Year

No

. o

f tr

an

sp

lan

ts

Thal Non Thal

Transplant activity of CMC Vellore, India

TOTAL TX ACCORDING TO DISEASE

0

2

4

6

8

10

12

14

MM NHL HL AML

total Auto SCT = 36 12 13 7 4

12

13

7

4

Total Auto SCT = 36 ( 2014-2018)

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AGE AND SEX DISTRIBUTION

16

58

Male

Female

Median age

35.74 Yrs

(16-58)

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ENGRAFTMENT( ANC>500, PLT>20,000) DAYS

0

5

10

15

20

25

Da

ys

co

un

t Neutrophil

Platelet

Case numbers

Neutrophil

engraftment

average 9.6 D

Platelet

engraftment

average 11.4 D

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OVERALL OUTCOME OF TX PATIENTS

Case Dx Status before

Tx

Mobilization Stem Cell

yield

Conditioning outcome

D100

Outcome

>D100

MM 12 CR, VGPR Cy-GCSF

>2x 106/Kg

Melphalan

200mg/m2

Alive, CR 7 relapsed,

> 10 month,

all survived

upto 1 yr>

death=05

NHL 13 CR RICE-GCSF

ICE-GCSF

BEAM Alive, CR 2 relapse.

All survived

CR

HD 07 CR, PR GND-GCSF

ICE-GCSF

BEAM Alive , CR 2 relapse

All CR, SD.

01 death.

AML 04 CR HiDAC-GCSF Bu-Cy Alive , CR Alive , CR

01 death.

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SURVIVAL AT A GLANCE

0 10 20 30 40 50 60

1

4

7

10

13

16

19

22

25

28

31

34

Survival in months

Dead

Alive

NO TRM In

D 100

Months

Ca

se n

um

be

rs27

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OUT COME AT DMCH BMT CENTER

60%

62%

64%

66%

68%

70%

72%

74%

76%

2 yr OS 2 Yr PFS

75%

66.00%

Survival

Survival

• Median observation period 20.85 months( 2-56 m).

• No TRM within 100 Days

• Less relapse from Non Hodgkin Lymphoma patients.

• MM relapse average >1.2Years.

• All death had Relapse + infection.

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MAJOR COMPLICATIONS

3630

3

4

13

6

6

2

3

1

1

0 10 20 30 40

Neutropenic Fever

Mucositis G I-II

severe Vomiting

Pneumonia

Bacteremia

Sepsis Nor support

severe diarrhoea

C diff colitis

Grade III-IV mucositis

Respiratory Failure

Ventilator support

Major early complications

major complications

P. aeruginosa

S. epidermidis

MRSA

Klebsiella

Acinatobacter

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OTHER CENTERS ACTIVITY

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Name of centre Number of Auto Tx start of activity

DMCH 36 2014

Apollo Hospitals Dhaka 07 2016

Dhaka CMH 12 2016

BSMMU 01 2018

GOAL & VISION

Improved Cancer Care

Laboratory facilities , molecular testing

HLA lab & National Donor registry

Allogeneictransplant Center

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2015 national

donor registration

RELATIVE LOW COST OF TX AT BANGLADESH 32

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Type of Tx Bangladesh India*

Autologous Stem cell

transplant

6000-8000 $ USD, $ 12,500 (range $

10,331–39,367)

Allogeneic stem cell

transplant

10,000-12,000 $ $ 17,914 (range $

10,832–44,701).

*Mediterr J Hematol Infect Dis. 2014

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•2017 ASH : Digital poster award

and publication in ‘Blood

Advances’.

• 2 more articles in ‘Journal of

Global Oncology’ .

•ASH VTP award on BMT

Achievements!

TAKE HOME MESSAGES

Extreme dedication and strong TEAM work is the key to run BMT unit.

36 ASCT have been done at DMCH BMT unit.

No TRM in 100D so far.

2 year OS is 75%.

Challenges in every steps of running BMT. [ *Financial constrain is a major challenge].

Extensive and continuous government support is necessary for running this program.

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ACKNOWLEDGEMENT 35

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All the departments are involved directly or indirectly.

• Department of Anesthesiology

• Department of Nephrology

• Department of Radiology

• Department of Microbiology

• Department of Medicine and all allied subject

THANK YOU

FURTHER READING 1. Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lions N, et al. Ifosfamide, carboplatin and etoposide: A

highly effective cyto-reduction and peripheral blood progenitor cell mobilization regimen for transplant-eligible patients with non-Hodgkins lymphoma. J Clin Oncol. 1999;17:3776–85. [PubMed]

2. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy sensitive non-Hodgkin lymphoma. N Engl J Med. 1995;333:1540–5. [PubMed]

3. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologoustransplantation for relapsed large B-Cell lymphoma in the Rituximab Era. J Clin Oncol. 2010;28:4184–90. [PMC free article] [PubMed]

4. Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol.2005;23(22):5027-5033.

5. Friedberg JW. Rituximab for early-stage diffuse large-B-cell lymphoma.LancetOncol.2006;7(5):357-359.

6. Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era J Clin Oncol28:4184-4190. © 2010 by American Society of Clinical Oncology/ Guglielmi C, Gomez F, Philip T, et al: Time to relapse has prognostic value in patients with agressive lymphoma enrolled onto the Parma trial. J Clin Oncol 16:3264-3269, 1998

7. Blay J, Gomez F, Sebban C, et al: The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: Analysis of the PARMA trial. Parma Group. Blood 92: 3562-3568, 1998

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