Survival benefit of lung transplant for cystic fibrosis since lung allocation score implementation

Abstract

Rationale: The survival benefit of lung transplantation (LT) in adult patients with cystic fibrosis (CF) is debated.

Objectives: We sought to assess the survival benefit of LT in adult patients with CF.

Methods: We used data from the United Network for Organ Sharing Registry to identify adult patients with CF on a wait list for LT in the United States between 2005 and 2009. Survival times while on the wait list and after LT were modeled by use of a Cox model that incorporated transplantation status as a time-dependent covariate. Evolution in lung allocation score (LAS) while on the wait list was used as a surrogate for disease severity. We fitted a model for the joint distribution of survival and longitudinal disease process (LAS over time).

Measurements and main results: A total of 704 adult patients with CF were registered on a wait list during the study period. The cumulative incidence of LT was 39.3% (95% confidence interval, 35.6-42.9%) at 3 months and 64.7% (61.0-68.4%) at 12 months, whereas the incidence of death while on the wait list at the same times was 8.5% (6.4-10.6%) and 12.9% (10.3-15.5%), respectively. Survival after LT was 96.5% (94.7-98.2%) at 3 months; 88.4% (85.1-91.8%) at 12 months; and 67.8% (59.9-76.8%) at 3 years. LT conferred a 69% reduction in the instantaneous risk of death (51-80%). The interaction between LAS and LT was significant: the higher the LAS, the greater the survival benefit of LT (P < 0.001).

Conclusions: LT confers a survival benefit for adult patients with CF.

Figure 1.

Kaplan-Meier estimator (with 95% confidence interval) for survival after lung transplantation for the 454 patients.

Figure 2.

Hazard ratio for lung transplantation survival effect (with 95% confidence interval) by lung allocation score measured at registration for the wait list. Hazard ratio below 1 indicates a survival benefit.

Figure 3.

Conditional probability of surviving later times than the last observed time for which a longitudinal measurement was available with (red) or without (black) a lung transplant. These probabilities are computed based on the true lung allocation score (LAS) history of one of the patients enrolled in this study. Expected survival is computed at each time a LAS measurement is available (asterisks). The black curve on the left is the fit of the mixed-effect model.