1. Reconditioning Donor Lungs for Transplantation Andrew Fisher
Professor of Respiratory Transplant Medicine
Academic Director
Institute of Transplantation
Freeman Hospital, Newcastle Upon Tyne

2. Worldwide Adult Lung Transplants
J Heart Lung Transplant.  2012 Oct; 31(10):

3. Lung Transplant Activity Freeman Hospital 1985-2013

4. Outcome of 258 UK patients listed for lung transplantation 2009-2010
31%
NHS Blood and Transplant

5. Waiting Time to Lung Transplant by ABO blood group
NHS Blood and Transplant Activity Report

6. UK Donor Utilisation for Lung Transplantation 2001-2012
Data from NHS Blood and Transplant 2012

7. Extended Criteria Donor Lungs
Botha, Fisher et al, Transplantation 2006

8. Donor Lung Assessment Visual Radiological Functional Physiological
oxygenation
Physiological
haemodynamics
ventilation
metabolic
Microbiological
Biological

9. 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

10. Ex-Vivo Lung Perfusion
Ventilator
Perfusate
Reservoir
Reservoir
Leukocyte Depleting Filter
PA outflow
LA inflow
Pump
Membrane Gas Exchanger

11. Described successful reconditioning and transplantation of
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 Jan;87(1):

12. Establishing an EVLP Programme in 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

13. Courtesy of Ms Karen Redmond (Harefield Hospital)
At start of EVLP
At end of EVLP
Bilateral pulmonary congestion on the first radiograph. Pulmonary congestion improves on the second radiograph.
Courtesy of Ms Karen Redmond (Harefield Hospital)

14. EVLP Good Ventilatory Performance

15. EVLP Poor Ventilatory Performance

16. Ex-vivo Metabolism

17. Ex-vivo Metabolism

18. Gas assessment after EVLP

19. 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

20. Normothermic ex vivo lung perfusion in clinical lung transplantation New England Journal of Medicine 2011; 364(15), p 1431–1440.
Professor Shaf Keshavjee

21. 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

22. Commercial EVLP Systems
Transmedics
OCS system
X-VIVO System
Vivoline System

23. A Study of Donor Ex-vivo Lung Perfusion in United Kingdom Lung Transplantation
DEVELOP-UK

24. DEVELOP-UK Freeman Hospital
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)
Freeman
Hospital
Wythenshawe
Hospital
Queen Elizabeth
Hospital
Papworth
Hospital
DEVELOP-UK
Harefield
Hospital

25. 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

26. 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.

27. 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

28. Institute of Transplantation Freeman Hospital, Newcastle Upon Tyne
Acknowledgements
Newcastle EVLP Clinical Research Team
Professor John Dark
Dr Anders Andreasson
Mr Stephen Clark
Dr Mahesh Prabu
Professor Paul Corris
Mr Tanveer Butt
Mrs Gail Johnstone
Retrieval Surgeons
Transplant Surgeons
Transplant Co-ordinators
Perfusionists
Theatre Nurses
Institute of Transplantation
Freeman Hospital, Newcastle Upon Tyne
Thanks to all our Patients
waiting for a lung transplant
DEVELOP-UK