A practical approach to ABO-incompatible heart transplantation from the Pediatric Heart Transplant Society (PHTS)

ABO-incompatible (ABOi) heart transplantation, first performed in infants by West and colleagues in 1996, transformed pediatric heart allocation by challenging longstanding immunologic constraints. Early success of this approach leveraged the developmental immaturity of the neonatal immune system and has since shown comparable short- and long-term outcomes to ABO-compatible (ABOc) transplantation. Over three decades, increasing clinical experience and policy evolution, including broader ABOi eligibility criteria and relaxed titer thresholds, have expanded access to donor hearts and reduced waitlist mortality, particularly among blood group ABO-O candidates. Despite these advances, marked variability persists among centers in the measurement, interpretation, and reporting of ABO antibody titers, directly influencing candidate selection, perioperative management, and post-transplant surveillance. Most assays rely on manual hemagglutination techniques that are subject to significant inter-laboratory and intra-laboratory variability. Emerging single-antigen bead-based methods utilizing the Luminex™ platform may provide an opportunity for standardized, semi-quantitative assessment of graft-relevant anti-A and -B antibody levels. Perioperative strategies are individualized according to ABO antibody titer, with intraoperative plasma exchange or immunoadsorption typically employed when titers exceed a center-specific level. Standard immunosuppression regimens are generally sufficient, with anti-B cell therapies (e.g., rituximab) reserved for elevated or rebound titers. Long-term outcomes remain excellent, with most patients not producing donor-specific ABO antibodies after ABOi transplant. Most centers perform surveillance biopsies only when rising titers, an uncommon occurrence, are accompanied by graft dysfunction or biopsy-proven antibody-mediated rejection, managed with combinations of plasmapheresis, IVIG, and anti-B cell therapies as indicated. Future multicenter collaborations incorporating standardized reporting and longitudinal follow-up will be critical to optimize candidate selection, refine management algorithms, and further improve utilization and outcomes of ABOi heart transplantation.