Reconditioning Donor Lungs for Transplantation

Andrew FisherProfessor of Respiratory Transplant Medicine

Academic Director Institute of Transplantation

Freeman Hospital, Newcastle Upon Tyne

Worldwide Adult Lung Transplants

J Heart Lung Transplant.  2012 Oct; 31(10): 1045-1095

Lung Transplant ActivityFreeman Hospital 1985-2013

32

46

61 63

5534

11 6

14

7 9

12 1621 22

0

10

20

30

40

50

60

70

80

90

100

6 months 1 year 2 years 3 years

Time since listing

Pe

rce

nta

ge Died

Removed

Still waiting

Transplanted

Post-registration outcome for 258 new lung only registrations made in the UK, 1 April 2009 - 31 March 2010

Figure 4

Outcome of 258 UK patients listed for lung transplantation 2009-2010

31%

NHS Blood and Transplant

Waiting Time to Lung Transplantby ABO blood group

NHS Blood and Transplant Activity Report 2011-2012

Data from NHS Blood and Transplant 2012

UK Donor Utilisation for Lung Transplantation 2001-2012

Extended Criteria Donor Lungs

20 – 45 65

>350 >300Donor

OptimisationPulm. Vein

Gas200

NeverCumulative Current

Clear Donor Optimisation Persistent CollapseDense Consolidation

Pan resistant OrganismMycobaterial Disease

Antibiotics HIV+Culture Negative

NeurogenicPulm Edema

<55 60

? Upperlimit

ClearPurulent Inflammation Aspiration Visualised

Tumour

Bronchoscopy

appearance

Microbiology

Chest x-ray

Smoking

History

PO2/FiO2

Age

(years)

Indicator “Ideal”Donor

“Standard”Criteria

Marginal DonorProgression

“Unusable”Donor

Non-Purulent

Gram-stain Negative

Clear

<20 p.y.

Botha, Fisher et al, Transplantation 2006

Donor Lung Assessment• Visual• Radiological• Functional

– oxygenation

• Physiological– haemodynamics

– ventilation

– metabolic

• Microbiological• Biological

Objective Assessment of Donor Lung Acceptance

Outcome Age / yr PaO2/ FiO2 Neut. 103/ml IL-8 pg/l % culture positive

accepted

n = 14

36.7 63.2 44 810 9 (75)

excluded

n = 25

49.5

p=0.009

43.1

p=0.001

46

p=0.78

540

p=0.64

9 (43)

p=0.1

Selection criteria poor discriminators of injury and infection leading to exclusion of potentially usable lungs.

Fisher et al, Thorax 2004;59:434

Ex-Vivo Lung Perfusion

Ventilator

Reservoir

PumpMembrane Gas Exchanger

Leukocyte Depleting

FilterPA outflow

LA inflow

Perfusate Reservoir

Professor Stig Steen

Described successful reconditioning and transplantation of 6 out of 9 donor lungs deemed unusable for transplant. All 6 recipients survived the first 3 months 4 of the 6 were alive and well 12 months after transplant

Ann Thorac Surg. 2009 Jan;87(1):255-60.

Establishing an EVLP Programmein Newcastle

•Ethics committee approval•Hospital procedure approval•Non-clinical pilot phase•Consent of waiting list patients•Education of the transplant team•Manpower and logistics•Deciding the technique•Agreeing acceptance criteria

Courtesy of Ms Karen Redmond (Harefield Hospital)

At start of EVLP At end of EVLP

EVLP Good Ventilatory Performance

EVLP Poor Ventilatory Performance

Ex-vivo Metabolism

Ex-vivo Metabolism

Gas assessment after EVLP

Potential Impact of EVLP

• Increased offering of donor organs• Increased lung transplant activity• Reduced waiting list mortality• Reduced incidence of severe PGD?• Improved longterm outcomes?

– Less rejection?– Less infection?

• Platform for therapeutics

Normothermic ex vivo lung perfusion in clinical lung transplantation

New England Journal of Medicine 2011; 364(15), p 1431–1440.

Professor Shaf Keshavjee

Normothermic ex vivo lung perfusion in clinical lung transplantation

New England Journal of Medicine 2011; 364(15), p 1431–1440.

Phase I non-randomised safety study (n=20) XVIVO Perfusion System Completion date February 2010 Outcomes in the EVLP group were comparable to that

achieved with standard transplants: 15% incidence of Primary Graft Dysfunction (PGD) in EVLP

group at 72 hrs 30% incidence of PGD in the standard transplant group p=0.11

Commercial EVLP Systems

X-VIVO SystemVivoline SystemTransmedics OCS system

A Study of Donor Ex-vivo Lung Perfusionin United Kingdom Lung TransplantationA Study of Donor Ex-vivo Lung Perfusionin United Kingdom Lung Transplantation

FreemanHospital

PapworthHospital

HarefieldHospital

Queen Elizabeth Hospital

WythenshaweHospital

Andrew Fisher Chief Investigator (Newcastle)

Karen Redmond Surgical Lead (Dublin)Andre Simon PI (Harefield)Nizar Yonan PI (Manchester)Steven Tsui PI (Papworth)Jorge Mascaro PI (Birmingham)John Dark PI (Newcastle)Nandi Marczin ITU Lead (Imperial College)

Study Details• Design:

- Non-randomised, non-inferiority observational study with an adaptive design

• Funders: - NIHR Health Technology Assessment

Programme and CF Trust• Sponsor:

- The Newcastle upon Tyne Hospitals NHS Foundation Trust

Primary Objective:

To compare survival during the first 12 months after lung transplantation in recipients of EVLP assessed and reconditioned donor lungs (treatment group) compared to that of recipients of standard donor lungs (control group), in order to assess whether survival in the EVLP treatment group over that period is non-inferior to that in the standard control group.

Secondary Objectives:

• Assess early clinical outcomes• Measure quality of life (QOL)• To determine if EVLP is a cost-effective• Explore patients attitudes to and experiences

of EVLP• To collect biological samples during EVLP

reconditioning to support parallel mechanistic studies

Acknowledgements

Newcastle EVLP Clinical Research TeamProfessor John DarkDr Anders AndreassonMr Stephen ClarkDr Mahesh PrabuProfessor Paul CorrisMr Tanveer ButtMrs Gail Johnstone Retrieval SurgeonsTransplant SurgeonsTransplant Co-ordinatorsPerfusionistsTheatre Nurses

Thanks to all our Patientswaiting for a lung transplant

Institute of TransplantationFreeman Hospital, Newcastle Upon Tyne