Impact of ABO compatibility on outcomes after allogeneic hematopoietic cell transplantation (HCT): increased risk of acute GVHD with ABO bidirectional mismatch, independent of traditional and emerging GVHD prophylaxis strategies.

Abstract

The impact of ABO incompatibility on outcomes after allogeneic hematopoietic cell transplantation (HCT) remains unclear, with both positive and negative associations reported between ABO mismatch and overall survival (OS), nonrelapse mortality (NRM), engraftment, and graft-versus-host disease (GVHD). The impact of ABO incompatibility on transplant outcomes, in the setting of traditional and emerging GVHD pharmacologic strategies, is worthy of further study. We performed a single-center analysis of first allogeneic HCT (2012-2022) and correlated outcomes with donor-recipient ABO compatibility (classified as compatible, major, minor, bidirectional). Kruskal-Wallis, Fisher's exact, and Chi-squared tests were conducted for comparing patient characteristics among the 4 cohorts. Competing risk analyses with cumulative incidence curves and Gray's test were conducted for comparing post-HCT time-to-event outcomes. Total 715 allogeneic HCT recipients were included: 396 ABO compatible, 150 minor incompatible, 125 major incompatible, and 44 bidirectional mismatched. Mobilized peripheral blood stem cells (PBSC) were the most common graft source, with cord blood grafts less likely to be ABO compatible than PBSC or marrow (P = 0.05). There was a significant association between donor relation and degree of ABO match (P < 0.001); type of GVHD prophylaxis also was significantly associated with ABO match (P = 0.013). There was no significant difference in conditioning intensity among the ABO cohorts (P = 0.068), nor in year of HCT (P = 0.53). The distribution of donor HLA-type was different among the cohorts (P < 0.001): HLA-matched unrelated donors (URD) were the most common donor across all 4 cohorts. By analyzing HCT outcomes by degree of ABO match, there was no significant association between ABO compatibility and the cumulative incidence of engraftment of neutrophils to ≥500/µL (P = 0.911), or platelets to ≥20 × 10⁹/L (P = 0.566); no significant differences were identified in the cumulative incidence of relapse (P = 0.897), OS (P = 0.535), or chronic GVHD (P = 0.866). The ABO bidirectional mismatch cohort had a higher risk of acute GVHD (HR = 1.49) compared to the ABO compatible cohort (95% CI: 1.00-2.21, P = 0.048). After HCT, we found a higher hazard of acute GVHD for the ABO bidirectional mismatch cohort compared to the compatible cohort, but no significant impact of ABO compatibility on engraftment, chronic GVHD, relapse, or OS. However, when also considering the impact of GVHD prophylaxis regimens including the newer standard of care regimen of PTCy, we identified significant associations of GVHD prophylaxis, not ABO compatibility, with the outcomes of engraftment, acute GVHD, and OS. A larger multi-center study of ABO compatibility in HCT, incorporating newer GVHD algorithms, is merited.