Reconditioning Donor Lungs for Transplantation Andrew Fisher Professor 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 Activity Freeman Hospital 1985-2013

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

Waiting Time to Lung Transplant by ABO blood group NHS Blood and Transplant Activity Report 2011-2012

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

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

Donor Lung Assessment Visual Radiological Functional Physiological 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 Perfusate Reservoir Reservoir Leukocyte Depleting Filter PA outflow LA inflow Pump Membrane Gas Exchanger

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

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

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)

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 Transmedics OCS system X-VIVO System Vivoline System

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

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

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

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