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A Tale of Two Systems: Adult Lung Allograft Allocation Across the World


Omar H. Mohamedaly, MD
Duke University
Durham, NC, USA
Omar.mohamedaly@duke.edu

Caroline M. Patteron, BMBS, BMedSci, MRCP
Papworth Hospital NHS Foundation Trust
Cambridge, UK
Carolinemariepatterson@nhs.net



First, two disclaimers: 1. There are probably almost as many nuanced versions of a lung allograft allocation system as there are countries (or cooperative groups of countries) performing lung transplantation; however, existing systems can generally be categorized according to whether or not they center on a net-benefit assessment. 2. While not exactly a tale of "the best of times" and "the worst of times," [1] the analogy holds true considering that we might be entering a new phase of streamlining and improving lung allograft allocation in a scientifically and ethically sound fashion.

Now that the disclaimers are out of the way, we can start with the United States model, which is perhaps the most scrutinized since the introduction of the Lung Allocation Score (LAS) in May 2005 [2]. The LAS replaced the previous model in which the length of time accrued on the waiting list was the primary determinant of allograft allocation with one based on "net transplant benefit," a measure based on waiting list and expected post-transplant survival probability. In doing so, the goal was to de-emphasize waiting list time and geography and emphasize transplant urgency (a measure of which is factored twice in the LAS) in order to reduce waiting list mortality and avoid inappropriate or futile transplants. Standardization was intended to increase allocation transparency and allow periodic data analysis to continually refine the LAS and its component variables [2,3], as occurred to great fanfare in February 2015 [4].

Although a full discussion of the impact of LAS is beyond the scope of this article, the consequences of the new system were a 54% reduction in the number of candidates on the waiting list [5] (as the perceived need to list patients pre-emptively to allow for time accrual was obviated) and a reduction in the median time on the waiting list from over 2 years to consistently under 200 days [5]. The LAS also contributed to a 3-fold increase in transplants in ICU patients who previously would not have accrued sufficient time on the waiting list. Similarly, allocation based on net benefit resulted in IPF surpassing COPD as the leading indication for transplantation5. Perhaps most significantly, the mortality on the waiting list decreased, fulfilling one of the main goals of the LAS, with absolute death counts declining from around 500 to under 300 a year and death rates per 1000 patient-years declining by 46% [5]. Although overall 1-year mortality remained stable post-LAS, reduced waiting list mortality came at the expense of increased perioperative morbidity and mortality among patients with high LAS [6].

The American experience led to consideration of the LAS for adoption more globally. Germany was the first country to adopt the LAS in December 2011, replacing a 3-tier system in which waiting list time determined order of transplant within each of the 3 tiers (highly urgent/ICU patients, urgent/hospitalized patients, and elective transplants) with the LAS [7]. A concurrent system of rescue allocation was adopted to allow the transplant of previously rejected organs into regional recipients regardless of LAS and accounted for about one third of procedures. Despite the potential dilutional effects of rescue allocation, the German LAS experience was fairly similar to the US experience with an increase in transplants for IPF and critically ill patients, a 23% reduction in waiting list mortality (although interestingly not for the IPF subgroup), and unchanged 3-month survival post-transplant [7].

Given the cooperation between Germany and 7 other European countries (Austria, Belgium, Croatia, Hungary, Luxembourg, the Netherlands, and Slovenia) as part of Eurotransplant [8], the German adoption of the LAS was somewhat of a gateway for the LAS in Europe: From December 2011, all countries within Eurotransplant agreed to enter LAS data on all highly urgent patients, arbitrarily defined as those with an LAS of 50 or above, for the international exchange of allograft offers. Subsequently, the Netherlands became the second country to officially adopt the LAS in April 2014. International allocation in Eurotransplant now proceeds as follows [8]: Patients with a high LAS from a country with a negative total balance with the donor country are positioned at the top of the donor country's match list, while those with a low LAS from a country with a negative total balance with the donor country are sorted among the donor country's patients according to LAS in the case of a German or Dutch donor or waitlist time in the case of non-LAS donors.

Despite differences in donor availability and competing national interests, international collaboration on organ exchange is a necessary reality of lung transplantation in smaller countries and has been shown to increase transplant activity and reduce waiting list mortality [9] within necessary constraints to minimize ischemic time. Such collaboration will likely pave the way for wider LAS adoption; this is most imminent in the Eurotransplant zone, where interest is growing in identifying factors predictive of mortality in all patient groups beyond waiting list time [10,11]. LAS and a modified LAS (called LASplus and including additional clinical factors such as ECMO, non-invasive ventilation, pneumothorax, and hemoptysis requiring bronchial artery embolization) have recently been validated as mortality predictors in Eurotransplant highly urgent and urgent patients, leading to the proposal of these net-benefit scores "as the basis for a new lung allocation policy in Eurotransplant" [11].

While other countries have not officially endorsed use of the LAS or similar net-benefit scores quite yet, there has been a trend of modifying waiting list policies to facilitate emergent transplants in patients who deteriorate and require mechanical ventilation or ECMO. So-called high-emergency allocation was instituted in France [12] and Switzerland [13] in July 2007 and more recently in Italy in November 2010 [14,15] with a significant increase in ICU transplants with lower, albeit acceptable mid-term survival. A similar trend has been seen in Canada, where some centers have added a third level of urgency to expedite transplantation of rapidly deteriorating patients whose urgency is not adequately defined by the existing 2-status classification of stable vs. deteriorating [16]. Scandiatransplant, the cooperative group regulating transplantation in Denmark, Finland, Iceland, Norway, and Sweden, places patients on mechanical ventilation at the top of the shared waitlist [17,18].

The regulatory agency for transplantation in the United Kingdom, National Health Service Blood and Transplant, allocates allografts "based on need, benefit, and other clinical issues" within the zonal boundaries of each transplant center (similar to US organ procurement organizations), though the selection of recipients from local waiting lists is left to the discretion of transplant center physicians when an offer is available [19]. Australian allocation follows the UK model with physician discretion brought into play if more than one candidate meets size and blood type compatibility criteria. On the extreme end of the spectrum is Japan, where allocation continues to be done on a "first come, first served" basis [20].

In conclusion, while it may be overly simplistic to think of a net-benefit, LAS-based system as the panacea solving all the problems of pure waiting list time-based allocation, especially considering the historic limitations of the LAS in adequately prioritizing PAH patients [21], eliminating all disparities in access to transplant [22], or focusing on waiting list mortality at the expense of long term outcomes [6] and resource utilization [24], such a system is at least a promising start in standardizing allocation with a strong scientific basis that is adaptive to changes in patient characteristics and open to incorporating additional survival predictors as those become validated [3,25]. We are also starting to see more discussion about the role geography should or should not play in lung allocation and how to optimize that role in countries like the United States, where a national waiting list may not be practical, but broader geographical sharing is increasingly advocated [26,27]. As such, we may in fact be ushering in "the best of times," in which lung allocation is more transparent, ethical, and more importantly predicated on maximizing patient benefit, while minimizing patient harm, ultimately the goal of all our endeavors in medicine. ■

Disclosure Statement: The authors have no conflicts of interest to disclose. However, the authors would like to thank Drs. Laurie Snyder and Jasvir Parmar for their critical appraisal of this article.


References:

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