Equivalent Outcomes for Pediatric Heart Transplantation Recipients: ABO-Blood Group Incompatible versus ABO-Compatible

Abstract

ABO-blood group incompatible infant heart transplantation has had excellent short-term outcomes. Uncertainties about long-term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABOincompatible recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart transplantation recipients (≤14 months old, 1996-2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor-specific antibodies against blood group antigens, in only two ABO-incompatible patients were these antibodies implicated in antibodymediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow-up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABOblood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO-compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor-specific isohemagglutinins and the implications for graft accommodation are warranted.

Current state of pediatric cardiac transplantation

“…Looking at ABO-incompatible listing as a strategy, failure to list for an ABO-incompatible graft and high clinical status emerged as the only factors associated with mortality (18). Multiple publications have now shown equivalent outcomes for ABO-incompatible heart transplantation, including rejection, co-morbidities, CAV, and graft survival (19)(20)(21). From an immune perspective, the observations about production of donorspecific isohemagglutinins or lack thereof has provided insight and impetus for further study into mechanisms of B cell tolerance (22).…”

Pushing the boundaries: The current status of ABO-incompatible cardiac transplantation

“…15,35,37 Isohemagglutinin titers should be measured regularly in the immediate post-transplant period but correlate poorly with clinical, echocardiographic or pathologic signs of AMR. One explanation for this may be that antibodies bind to the graft and thereby decrease the circulating titer.…”

“…6,37,40,47,53 There appears to be no difference in longer term survival, nor an increased incidence of cardiac allograft vasculopathy, post-transplant lymphoproliferative disease (PTLD) or renal dysfunction. 35,48 A recent multicenter study using the Pediatric Heart Transplant Study (PHTS) database analyzed 85 ABOi cardiac transplants. The study confirmed these single-center findings with equivalent 1-year survival and freedom from rejection when compared with ABOc transplants.…”

“…Peri-transplant management differs in sensitized patients and standard practice includes blood volume exchange on bypass until titers are low. 15,35 Although not universal, immediately post-transplant, plasmapheresis (PP) or immunoadsorption (IA) is used by some institutions for 5 to 7 days.…”

“…All patients underwent blood volume exchange on bypass, which is now standard practice. 35 Immunosuppressive therapy post-transplant and protocol biopsy for rejection surveillance were standard for the institution. Splenectomy was not performed, but infants routinely undergo thymectomy at cardiac surgery (including transplantation), and therefore may have subsequently impaired T-lymphocyte-mediated responses to antigenic stimulation.…”