Combined Effect of Unrelated Donor Age and HLA Peptide-Binding Motifs (PBM) Match Status on HCT Outcomes

An HLA-mismatched unrelated donor (MMUD) who is class I protein binding motifs (PBM)-matched is preferred over a PBM-mismatched donor. We hypothesized that using a younger donor (<35 years vs >35 years) could compensate for the inferior overall survival (OS) associated with PBM-mismatches. We compared six groups: HLA-matched/younger donor (n=10,531), HLA-matched/older donor (n=3572), PBM-matched/younger donor (n=357), PBM-matched/older donor (n=257), PBM-mismatched/younger donor (n=616), and PBM-mismatched/older donor (n=339) in patients undergoing transplantation with conventional graft-versus-host disease (GVHD) prophylaxis. In multivariate analysis, HLA-matched/younger donors were associated with superior OS relative to any other group. Pairwise comparisons showed that donor age significantly impacted OS in both HLA-matched and HLA-mismatched groups. Moreover, younger donors appeared to negate the detrimental effect of PBM-mismatching: the PBM-matched/younger donor group had similar OS as the HLA-matched/older donor group and the PBM-mismatched/younger donor group had similar OS as the PBM-matched/older donor group. Our study suggests that older unrelated donor age and PBM-mismatching confer similarly adverse effects on OS and the impacts are additive - a finding which may widen the "acceptable" donor pool. The best OS is observed with HLA-matched/younger donors and the worst with PBM-mismatched/older donors. These findings should be validated with other datasets and with post-transplantation cyclophosphamide-based prophylaxis.