A multi-institutional evaluation of antibody-mediated rejection utilizing the PHTS database: Incidence, therapies, and outcomes

Background Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. Methods We queried the PHTS database for patients < 18 years undergoing primary HT between 1/2010 - 12/2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies, and survival were analyzed. Results An episode of AMR was identified in 179/1596 (11%) HT recipients and 246/705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182/246 episodes and by immunotherapy in 64/246. Mixed rejection was identified in 179 episodes. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIG) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%), and eculizumab (0.4%). The most commonly used combination of therapies included IVIG/plasmapheresis/rituximab (13%). Thirty-three (16%) died after developing AMR. Patient and graft survival were lower for the AMR + group. One and 3 year survival after initial AMR diagnosis was 88% and 77%. Conclusions We report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.