Prevalence and Impact of Recurrent Rejection on Pediatric Heart Transplant Recipients: A PHTS Multi-Institutional Analysis

Abstract

Background: Studies evaluating the prevalence and impact of recurrent rejection (RR) in pediatric heart transplant (HT) are sparse.

Objectives: The purpose of this study was to describe prevalence and impact of RR on cardiac allograft vasculopathy (CAV) and graft loss after pediatric HT.

Methods: Data on HT from January 1, 2000, to June 30, 2020, in the Pediatric Heart Transplant Society database were included. Freedom from RR (≥2 rejection episodes) was compared by era (early: 2000-2009; current: 2010-2020). Outcomes for children experiencing RR were compared with those experiencing 0 or 1 rejection episodes and by type of RR (antibody-mediated rejection [AMR], acute cellular rejection [ACR], mixed [ACR/AMR]).

Results: Of 6,342 HT recipients, 1,035 (17%) experienced RR. In the current era, pediatric HT recipients were less likely to experience RR (P < 0.001). Freedom from CAV was similar for those experiencing RR to those experiencing 0 or 1 episode (96.6% vs 95.3% vs 96.6%); and similar regardless of the type of RR (AMR, ACR, or mixed) (65.5% vs 82.9% vs 100%) (P > 0.05). Freedom from graft loss was significantly lower for those experiencing RR to those experiencing 0 or 1 episode (56.3% vs 72.3% vs 82.3%) and lower for those experiencing recurrent mixed rejection or recurrent AMR compared with those experiencing recurrent ACR (65.3% vs 50% vs 81.8%). Black children experiencing RR subsequently had lower freedom from CAV and graft loss than White children (P < 0.05 for all).

Conclusions: Although prevalence of RR has decreased, children experiencing RR are at greatly increased risk for losing their graft, particularly those who have recurrent mixed or antibody-mediated rejection.

Keywords: acute cellular rejection; antibody-mediated rejection; cardiac allograft vasculopathy; graft loss; heart transplant; pediatric; recurrent rejection; transplant outcomes.