Validation of an EVLP Perfusate Diagnostic Test for the Prediction of Lung Transplant Outcomes

Purpose Ex vivo lung perfusion (EVLP) has become an invaluable tool in clinical lung transplantation (LTx). EVLP has enabled the assessment and rescue of donor organs that would have otherwise been discarded for LTx; however, determining which marginal organs are suitable for transplant remains challenging and relies largely on clinical assessment expertise. To this end, we describe our efforts to develop and validate a perfusate-based diagnostic test that will assist transplant teams in the EVLP decision-making process. Methods From 2008 to 2017, approximately 300 clinical EVLP cases were performed. A retrospective study was conducted using biobanked perfusate samples to develop and validate a set of biological mediators that predict: (i) whether a lung would be acceptable for transplant following EVLP; and (ii) the contribution of that donor lung to a favorable recipient outcome. A prospective study of an additional 50 EVLP cases is currently underway to further validate the EVLP predictive test. Results Using simple regression, a model that included donor characteristics and perfusate-derived mediators of inflammation (e.g., interleukin 6 and 8, and others) predicted whether or not a lung would be deemed acceptable for transplant with an overall accuracy of 70% [95% CI: 64-76%] (n=259). When the transplanted cases were further sub-stratified for recipient outcomes (e.g., ICU length of stay), our score's predictive performance improved to 83% [95% CI: 76-90%] (n=139). Next, a visual representation of the model was created and used in real-time alongside our clinical EVLP cases. In the ongoing test set of approximately 25 EVLP cases, the model accuracy is maintained at 71%. Conclusion We have developed and validated an EVLP test in the largest known cohort of EVLP cases to date. This score is able to predict whether a marginal donor lung will be acceptable for transplant following EVLP assessment. Furthermore, we can determine thresholds, independent of any recipient factors, that are associated with excellent transplant outcomes. This test represents a major step forward in the utilization of EVLP in lung transplantation by providing a useful metric that will better assist transplant teams to select lungs for successful outcomes on EVLP and subsequent transplantation.