Multiple Listing in Lung Transplant Candidates

A Cohort Study

Joshua J. Mooney; Lingyao Yang; Haley Hedlin; Paul Mohabir; Gundeep S. Dhillon

Disclosures

American Journal of Transplantation. 2019;19(4):1098-1108. 

In This Article

Discussion

A small number of US lung transplant waitlist candidates are multiple listed but those who are multiple listed have an increased likelihood of receiving a lung transplant compared to SL candidates. The majority of multiple listing registrations occurred in a different OPO than their initial listing OPO. The likelihood of being multiple listed was greater in candidates of younger age, female gender, white race, shorter stature, greater antibody sensitivity, lower LAS, or with a higher education level, or diagnosis of cystic fibrosis. Although being listed at multiple centers increased the likelihood of receiving a lung transplant, it was not associated with decreased waitlist mortality.

The factors associated with multiple listing included clinical factors that have been shown to influence waitlist outcomes, such as short stature, antibody sensitization, and LAS. Short stature is associated with reduced access to lung transplant and increased risk of waitlist death, which is related to the need to match candidates to donors of similar height and a smaller number of short stature donors than short stature candidates.[18] Multiple listing may therefore be used as a strategy for short stature candidates to increase access to a greater pool of short stature donors. Candidates with greater pretransplant human leukocyte antibody (HLA) sensitivity had a longer waitlist time and reduced access to lung transplant within a single center study.[19] Within our cohort, the need for a preliminary antibody crossmatch served as a surrogate for greater HLA antibody sensitivity due to the absence of alternative information, such as panel reactive antibodies or avoided antigens, within SRTR thoracic candidate standard analysis files. Therefore, similar to short stature, multiple listing may be used in candidates with greater antibody sensitivity to allow access to a greater pool of HLA compatible donors. The current lung allocation system does not adjust prioritization for short stature or highly sensitized candidates; broader geographic access to donor lungs or adjustments in LAS prioritization for short stature, or highly sensitized candidates may improve equitable access to transplant for these candidates, particularly candidates unable to pursue multiple listing. Notably, multiple listing was more common in candidates with lower medical urgency as measured by LAS rather than candidates with a higher LAS or high medical urgency. Candidates with a lower LAS have a lower risk of waitlist mortality and also intuitively have a lower transplant rate.[20] Therefore, multiple listing may also be used as a strategy to increase transplant likelihood for candidates with otherwise low transplant priority by their calculated LAS.

In renal, liver, and heart transplant candidates, socioeconomic factors including white race, higher education level, and private insurance have been associated with multiple listing.[6,11] Similarly, in our study white candidates and candidates with a college or postcollege degree were more likely to be multiple listed for lung transplant compared to nonwhite candidates and candidates with a high school or below level of education. Private insurance was more common in multiple listed candidates but was not statistically significant after adjusting for other factors associated with multiple listing. Our results suggest that multiple listing is a source of demographic and socioeconomic inequity in lung transplant access. We hypothesize that patients with a higher level of education are more likely to understand their right to be listed at multiple centers, understand the potential advantages of multiple listing, and have the means to allow multiple listing. The differences in multiple listing status by race may also explain previously described disparities in transplant access among nonwhite waitlist candidates.[21]

The socioeconomic factors associated with multiple listing and advantages of multiple listing seen in our study and previous solid organ studies on multiple listing raise the long-debated question of whether multiple listing is fair and in concordance with the Final Rule on organ allocation.[11,22] Multiple listing is not typically practiced or has been banned in other countries transplant allocation systems, such as Eurotransplant. Following the approval of the practice of multiple listing within the United States in 1987, there have been several national and local attempts to ban multiple listing including proposed national bans in 1988 and again in 1994-1995 that were not implemented.[7,23,24] In 1990, the state of New York banned transplant candidates who were already listed for organ transplant from subsequently registering on another waitlist within the state; however, its efficacy was limited by the inability to prohibit subsequent out-of-state transplant listings.[7,23] Regardless of future policy decisions on whether multiple listing should continue within the United States, understanding and addressing the underlying reasons why candidates pursue multiple listing are necessary to truly improve allocation equity for all. The majority of multiple listing candidates (82.1%) were listed in a different OPO than their initial listing OPO and thereby had access to another donor pool. This suggests that prioritized access to a broader geographic donor pool may have driven the decision for candidates to multiply list. Notably, there were specific transplant centers, OPOs, and OPTN regions with a greater proportion of the multiple listing registrations; however, only a minority of multiple listing candidates (43.7%) obtained their multiple listing at a center with a higher transplant rate. Therefore, although some candidates likely targeted multiple listing toward specific transplant centers (ie, one-third of multiple listing registrations were at five transplant centers), the decision to be multiple listed at a high transplant rate center was not universal.

Our results are limited by the observational nature of the study, in which differences in measured and unmeasured characteristics of SL and ML candidates may influence both the decision to multiple list as well as waitlist mortality and transplant outcomes. Although we performed a logistic regression model to identify the measured variables associated with multiple listing, there are likely additional unmeasured variables or confounders that are not available in registry data. There were missing data present, which we addressed through multiple imputations to mitigate the limitations of the missing data; however, results based on data are not as ideal as results based on fully observed data. To mitigate the differences in measured variables, SL and ML candidates were carefully matched on a number of demographic and clinical variables and the nonidentically matched characteristics were again adjusted for in our models to isolate the effect of multiple listing status on waitlist outcome. In analyzing the effect of multiple listing on waitlist outcomes, time zero was set as the time of multiple listing for the matched SL and ML candidates and the time spent prior to multiple listing was discarded. Although this approach has limitations, it was used instead of a time-dependent analysis to reduce bias as waitlist time differed between SL and ML candidates and candidates who do not survive long enough to become multiple listed would have contributed time to the model only as single listed candidates, whereas given sufficient time those candidates may have gone on to multiple listing.

In summary, our findings demonstrate that only 2.3% of lung transplant waitlist candidates are multiple listed with younger, female, white, short stature, highly sensitized, college or postcollege educated, lower LAS, and cystic fibrosis candidates more likely to be multiple listed. These multiple listed candidates have a greater likelihood of lung transplant than comparable single listed candidates. Addressing geographic and other clinical disparities in lung transplant access may help decrease the need and advantages of multiple listing and improve waitlist equity in lung transplant.

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