Prognostic impact of HLA supertype mismatch on outcomes after single-unit cord blood transplantation

Abstract Backgrounds: The “human leukocyte antigen (HLA) supertype” is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Methods: The clinical data of 1,603 patients who received sCBT in eight institutes in Japan between 2000 and 2017 were retrospectively analyzed. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. Results: An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. Conclusion: HLA-B supertype-matched grafts should be selected in sCBT.