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While CBT has a lower risk of graft\u2010versus\u2010host disease and requires less stringent histocompatibility, it is associated with a higher transplantation\u2010related mortality (TRM) compared to other donor sources. We hypothesized that assessing the immunogenicity of mismatched HLA could reveal non\u2010permissive mismatches contributing to increased TRM. We retrospectively analysed 1498 single\u2010unit CBT cases from 2000 to 2018 across eight Japanese institutions, evaluating the immunogenicity of mismatched HLA using the PIRCHE algorithm to examine binding affinities of HLA\u2010derived epitopes to donor or recipient HLA. Results indicated that Class I epitopes from mismatched recipient HLA\u2010B were significantly associated with poor outcomes due to higher TRM and lower neutrophil engraftment, particularly when presented on matched HLA class I. Notably, epitopes from HLA\u2010B exon 1 showed stronger prognostic significance, with HLA\u2010B alleles carrying M\u2010type leader peptides exhibiting higher affinity for these epitopes. Patients with a matched M\u2010type HLA\u2010B and Class I epitopes derived from mismatched HLA\u2010B exon 1 had worse outcomes. These findings suggest that immunogenicity\u2010informed donor selection could improve CBT outcomes.<\/jats:p>","DOI":"10.1111\/bjh.20035","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:41:43Z","timestamp":1741696903000},"page":"1406-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Indirect presentation of mismatched\n                    <scp>human leukocyte antigen<\/scp>\n                    \u2010B associates with outcomes of cord blood transplantation"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4270-1943","authenticated-orcid":false,"given":"Takeshi","family":"Sugio","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"},{"name":"Divisions of Oncology and Hematology, Department of Medicine Stanford School of Medicine  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