Abstract
Background: Antibody-mediated rejection (AMR) is of great relevance when assessing therapies to improve survival for pediatric heart transplant (HT). Biopsy (EMB) is the most specific means for diagnosing AMR. This study explores the impact on survival and adverse events after treated rejection (TRej) in children with AMR on EMB (any pAMR 1h or i, 2, or 3) vs acute cellular rejection (ACR). Methods: Children in the Pediatric HT Study transplanted between 1/2015-6/2022 who survived ≥2 weeks and had at least 1 TRej with EMB data were included. Survival was compared after 1st TRej with any AMR to pure ACR. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) after 1st TRej were assessed. Risk factors for mortality after AMR were identified using Cox proportional hazard modeling. Results: Among 3172 HT recipients, 906 (29%) had at least 1 TRej. Of these, 697 (77%) had EMB data to determine the presence of AMR. At the 1st TRej episode, 261 (37%) children had features of AMR. Median time to 1st Trej was earlier in those with AMR vs ACR, 0.11 vs 0.29 yrs. p=0.001. Survival after 1st TRej with AMR was worse than ACR in the 1st yr post HT (A); however, survival was similar when 1st TRej occurred after year 1 (B) (Figure 1 A, B). The AMR group had higher panel reactive antibody at HT, more congenital heart disease (CHD), and more had ABO incompatible HT (all p<0.05). There was no difference in time to 1st infection, malignancy, or CAV between those with treated AMR vs ACR. Multivariate predictors of graft loss after AMR were younger age, CHD, and ECMO at HT, and hemodynamic compromise at TRej (all p<0.048). Neither AMR grade nor concomitant ACR was associated with graft loss after AMR. Conclusion: This is the largest analysis of contemporary outcomes of EMB-confirmed AMR in pediatric HT. Findings underscore the impact of early AMR on graft loss and the need for tailored therapies. Similar time to infection after AMR vs ACR is notable since immune targets of therapy often differ.
Published Version
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