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Long-term Outcomes of Lung Transplant With Ex Vivo Lung Perfusion

Educational Objective To identify long-term outcomes after lung transplant recipients of donor lungs are treated with ex vivo lung perfusion.
Key Points

Question  What are the long-term outcomes of transplant recipients of donor lungs treated with ex vivo lung perfusion?

Findings  In this cohort study, donor lungs treated with ex vivo lung perfusion were more injured than conventional donor lungs, but there was no difference in survival or chronic lung allograft dysfunction between recipients of conventional donor lungs and donor lungs treated with ex vivo lung perfusion.

Meaning  During the era of ex vivo lung perfusion, transplant activity has increased without compromising outcomes in lung transplant recipients.

Abstract

Importance  The mortality rate for individuals on the wait list for lung transplant is 15% to 25%, and still only 20% of lungs from multiorgan donors are used for lung transplant. The lung donor pool may be increased by assessing and reconditioning high-risk extended criteria donor lungs with ex vivo lung perfusion (EVLP), with similar short-term outcomes.

Objective  To assess the long-term outcomes of transplant recipients of donor lungs treated with EVLP.

Design, Setting, and Participants  This retrospective cohort single-center study was conducted from August 1, 2008, to February 28, 2017, among 706 recipients of donor lungs not undergoing EVLP and 230 recipients of donor lungs undergoing EVLP.

Exposure  Donor lungs undergoing EVLP.

Main Outcomes and Measures  The incidence of chronic lung allograft dysfunction and allograft survival during the 10-year EVLP era were the primary outcome measures. Secondary outcomes included donor characteristics, maximum predicted percentage of forced expiratory volume in 1 second, acute cellular rejection, and de novo donor-specific antibody development.

Results  This study included 706 patients (311 women and 395 men; median age, 50 years [interquartile range, 34-61 years]) in the non-EVLP group and 230 patients (85 women and 145 men; median age, 46 years [interquartile range, 32-55 years]) in the EVLP group. The EVLP group donors had a significantly lower mean (SD) Pao2:fraction of inspired oxygen ratio than the non-EVLP group donors (348 [108] vs 422 [88] mm Hg; P < .001), higher prevalence of abnormal chest radiography results (135 of 230 [58.7%] vs 349 of 706 [49.4%]; P = .02), and higher proportion of smoking history (125 of 204 [61.3%] vs 322 of 650 [49.5%]; P = .007). More recipients in the EVLP group received single-lung transplants (62 of 230 [27.0%] vs 100 of 706 [14.2%]; P < .001). There was no significant difference in time to chronic lung allograft dysfunction between the EVLP and non-EVLP group (70% vs 72% at 3 years; 56% vs 56% at 5 years; and 53% vs 36% at 9 years; log-rank P = .68) or allograft survival between the EVLP and non-EVLP groups (73% vs 72% at 3 years; 62% vs 58% at 5 years; and 50% vs 44% at 9 years; log-rank P = .97) between the 2 groups. All secondary outcomes were similar between the 2 groups.

Conclusions and Relevance  Since 2008, 230 of 936 lung transplants (24.6%) in the Toronto Lung Transplant Program were performed after EVLP assessment and treatment. Use of EVLP-treated lungs led to an increase in the number of patients undergoing transplantation, with comparable long-term outcomes.

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Article Information

Accepted for Publication: July 7, 2019.

Corresponding Author: Jussi M. Tikkanen, MD, Toronto General Hospital, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada (jussi.tikkanen@uhn.ca).

Published Online: October 9, 2019. doi:10.1001/jamasurg.2019.4079

Author Contributions: Drs Divithotawela and Tikkanen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Divithotawela, Cypel, Martinu, Chow, de Perrot, Yeung, Keshavjee, Tikkanen.

Acquisition, analysis, or interpretation of data: Divithotawela, Cypel, Martinu, Singer, Binnie, Chow, Chaparro, Waddell, Pierre, Yasufuku, Donahoe, Keshavjee, Tikkanen.

Drafting of the manuscript: Divithotawela, Chow, Tikkanen.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Divithotawela, Cypel, Yeung, Tikkanen.

Obtained funding: Keshavjee.

Administrative, technical, or material support: Divithotawela, Cypel, Chow, de Perrot, Yasufuku, Keshavjee, Tikkanen.

Supervision: Divithotawela, Cypel, Martinu, Singer, Chaparro, Pierre, Keshavjee, Tikkanen.

Conflict of Interest Disclosures: Dr Cypel reported receiving personal fees from Lung Bioengeneering; and receiving funding from XOR Labs Toronto and Perfusix Canada outside the submitted work. Dr Waddell reported receiving grants from Canadian Institutes of Health Research and nonfinancial support from Xenios/Fresenius during the conduct of the study; and having a patent to US8247175132B2 issued, a patent to US9944950B2 issued, a patent to CA2944922A1 pending and licensed, a patent to CA2966282A1 issued, a patent to US10091986B2 issued and licensed, and a patent to WO201818100A1 issued. Dr de Perrot reported receiving personal fees from Bayer outside the submitted work. Dr Keshavjee reported receiving research funding from Perfusix Canada and XOR Labs Toronto; receiving grants from United Therapeutics outside the submitted work; and having a patent to XOR Lung Perfusion pending. Dr Tikkanen reported receiving nonfinancial support from Perfusix Canada during the conduct of the study; and personal fees from CSL Behring and Boehringer-Ingelheim outside the submitted work. Drs Cypel, Waddell, and Keshavjee are founders of Perfusix Canada. This company provides ex vivo lung perfusion (EVLP) services to University Health Network. Owing to conflict of interest relative to EVLP activities as lung transplant surgeons in the institution, Drs Cypel, Waddell, and Keshavjee do not receive any payments from Perfusix Canada. Furthermore, with respect to the provision of EVLP services, Perfusix Canada is a nonprofit company that does not generate profit from EVLP activities provided for University Health Network patients. Drs Cypel, Waddell, and Keshavjee are also founders of XOR Labs Toronto, a company dedicated to development of EVLP machines. The XOR Labs Toronto EVLP machine is in development phase and was not used in the performance of this study. Lung Bioengineering acquired Perfusix USA in 2015, a company that was cofounded by Drs Cypel, Waddell, and Keshavjee. Currently, Drs Cypel, Waddell, and Keshavjee are paid consultants for Lung Bioengineering. They give strategic advice to Lung Bioengineering lung perfusion center as members of its Scientific Advisory Board. The data in the current study were collected from consented University Health Network patients in a UHN Research Ethics Board–approved study. No other disclosures were reported.

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