Virtual Journal Club: Current State of Ex-Vivo Lung Perfusion

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INTRODUCTION

Lung transplantation is the preferred treatment for patients with end-stage lung disease. Worldwide, the number of lung transplants performed annually has steadily increased, with approximately 4000 lung transplants performed in 2013. Despite this growth, the number of lungs available for transplantation fails to meet the needs of those patients on the waiting list. In the United States alone, 2394 patients were newly listed in 2013 with a waitlist mortality rate of 15.1 per 100 patient years. The supply and demand mismatch is multifactorial, although one significant cause is the low rate of lung-specific organ utilization, which is the lowest among all transplanted organs. Only 15-25% of lungs from all potential donors are transplanted, compared to 30% of eligible hearts and 65-70% of kidneys and livers. Lungs, compared to other solid organs, are much more susceptible to a variety of injury mechanisms including direct trauma, aspiration, ventilator-associated pneumonia, pulmonary edema, acute lung injury from resuscitation, and neurogenic pulmonary edema. Ex-vivo lung perfusion (EVLP) has emerged as an essential platform for the reassessment, of lungs that initially did not meet transplantation criteria. We decided to review this report to summarize most recent clinical and research literature in ex vivo lung perfusion.

ABSTRACT
PURPOSE OF REVIEW:

The purpose of the current report is to review the ex-vivo peer-reviewed literature published in the last 5 years and to summarize the findings.

RECENT FINDINGS:

Encouraging data have been published by several centers utilizing ex-vivo lung perfusion (EVLP) as a means to identify viable grafts from the high-risk donor pool. The outcomes of transplanted lungs that were initially declined because of poor quality, but reevaluated with ex-vivo perfusion, are equivalent to standard criteria donor lungs. Further, research reports have emphasized the role of ex-vivo perfusion as a platform to improve graft quality and reduce the injurious effects of ischemia-reperfusion.

SUMMARY:

Over the last 10 years, EVLP has proved its value as a reassessment tool to increase donor utilization. As short- and long-term data demonstrate the safety of EVLP, its use as a therapeutic platform is emerging, along with the promise of a new era in lung transplantation.

Reference and link to full article:

Sanchez PG, Mackowick KM, Kon ZN. Current state of ex-vivo lung perfusion. Current Opinion in Organ Transplantation. 2016 Jun; 21(3): 258-266. To link to article, click here.

If you are unable to access the full article through the link, please email Hedi Aguiar – haguiar@odt-alliance.org.

DISCUSSION QUESTIONS
  1. Do you think that ex vivo lung perfusion can increase the percentage of transplanted lungs from the donor pool?
  2. By what means could ex vivo lung perfusion increase the percentage of transplanted organs?
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Comments

  1. Chris Jaynes  March 9, 2017

    I think this article summarizes the state of ex vivo lung perfusion (EVLP) very well. To date, most worldwide EVLP procedures have followed the Toronto protocol, which has (by far) the greatest adoption. Now that there are recipients of EVLP organs from the Toronto group who have been out nearly 9 years, we should see some interesting data on long-term outcomes and possible additional benefits of EVLP. This will hopefully encourage greater adoption of the technology.

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    • Wade Liu  March 11, 2017

      Thanks, Chris. Your comment actually spurred a question I had while reviewing the article. As a community, do we anticipate eventual standardization on a specific protocol (e.g., Toronto), or are there known and generally accepted scenarios or circumstances where other protocols might be better suited?

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      • Chris Jaynes  March 11, 2017

        Excellent question, Wade. FDA approves not only the device itself, but also the associated EVLP protocol. Since there is only one FDA-approved device for EVLP currently on the market (XVIVO XPS), the associated protocol (Toronto) is the most widely used and accepted to date. This could change if another device gets approved. Additionally, surgeons can use a device ‘off label’ and change up the protocol, but only if there was a compelling reason backed by strong evidence, which doesn’t currently exist.

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  2. Sharon Stover  March 11, 2017

    Thank you for your post. You stated the long-term data that will become available from the Toronto program might encourage greater adoption of the EVLP technology. The author indicates that, based on the available literature, the 3 lung perfusion methodologies available are safe and have produced positive results. However, the wider transplant community continues to question the safety and efficacy of EVLP, and its use seems to be limited to a small percentage of transplant programs, which subsequently limits the availability of long-term data. What other actions have been, or can be, taken to incentivize transplant programs’ participation in clinical trials in an effort to move this process forward at a faster pace?

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  3. Amy Clark  March 15, 2017

    EVLP technology seems to have enough positive outcomes to inspire further research based on Toronto and NOVEL trials with decent 1 yr survival. It will be interesting to see the transplant outcomes from the dedicated facility- based EVLP program. With this intense focus on ex-vivo perfusion, one can speculate that research in this field will develop into significantly improved outcomes. Another great feature of having this EVLP facility is removing the burden of each transplant center having to start/maintain it’s own program.

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  4. Kevin Myer  March 17, 2017

    With the presence of strong evidence supporting the use of EVLP, why is the actual update of this technology so slow? Yes it appears that this intervention can increase the availability of transplantable lungs. What are the barriers to broader use? Cost, competing instead of collaborating perfusion centers, regulatory barriers or lack of training? Other reasons? We should study this and discover ways to reduce these barriers to spread the technology.

    Wider application, better geographic access, shared cost might help increase the use of this technology.

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  5. Bill Thompson  March 20, 2017

    This article does a good job of summarizing Ex-Vivo and the experience of the Toronto group. The long term impact in the U.S. will take a substantial amount of long term research. I can imagine that transplant centers may be apprehensive of this new technology, learning to use it and applying it to their patient populations.

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