Effect of peptide‐binding motif on survival of <scp><i>HLA</i></scp>‐haploidentical transplantation with post‐transplant cyclophosphamide

<jats:title>Summary</jats:title><jats:p>Peptide‐binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in <jats:italic>HLA</jats:italic>‐haploidentical haematopoietic cell transplantation with post‐transplant cyclophosphamide (PTCy‐haplo). We therefore conducted a retrospective study using national registry data in PTCy‐haplo. Overall, 1352 patients were included in the study. PBM‐A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; <jats:italic>p</jats:italic> = 0.010). None of relapse, non‐relapse mortality (NRM) and graft‐versus‐host disease showed significant differences according to PBM‐A bidirectional mismatch status in the entire cohort. The impact of PBM‐A bidirectional mismatch on overall survival (OS) was preserved within the HLA‐A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM‐A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced‐intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM‐A bidirectional mismatch elevated the risk of mortality of PTCy‐haplo. Avoiding PBM‐A bidirectional mismatch might achieve better outcomes in PTCy‐haplo.</jats:p>