{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:14:16Z","timestamp":1792145656729,"version":"4.4.0"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Immunopeptidome divergence between mismatched HLA-DP is a determinant of T-cell alloreactivity and clinical tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched unrelated donor hematopoietic cell transplantation (UD-HCT). Here, we tested this concept in HLA-A, -B, and -C disparities after single class I HLA-mismatched UD-HCT. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> We studied 2,391 single class I HLA-mismatched and 14,426 fully HLA-matched UD-HCT performed between 2008 and 2018 for acute leukemia or myelodysplastic syndromes. Hierarchical clustering of experimentally determined peptide-binding motifs (PBM) was used as a proxy for immunopeptidome divergence of HLA-A, -B, or -C disparities, allowing us to classify 1,629\/2,391 (68.1%) of the HLA-mismatched UD-HCT as PBM-matched or PBM-mismatched. Risks associated with PBM-matching status were assessed by Cox proportional hazards models, with overall survival (OS) as the primary end point. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Relative to full matches, bidirectional or unidirectional PBM mismatches in graft-versus-host (GVH) direction (PBM-GVH mismatches, 60.7%) were associated with significantly lower OS (hazard ratio [HR], 1.48; P &lt; .0001), while unidirectional PBM mismatches in host-versus-graft direction or PBM matches (PBM-GVH matches, 39.3%) were not (HR, 1.13; P = .1017). PBM-GVH mismatches also had significantly lower OS than PBM-GVH matches in direct comparison (HR, 1.32; P = .0036). The hazards for transplant-related mortality and acute and chronic graft-versus-host disease but not relapse increased stepwise from full HLA matches to single PBM-GVH matches, and single PBM-GVH mismatches. A webtool for PBM-matching of single class I HLA-mismatched donor-recipient pairs was developed. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> PBM-GVH mismatches inform mortality risks after single class I HLA-mismatched UD-HCT, suggesting that prospective consideration of directional PBM-matching status might improve outcome. These findings highlight immunopeptidome divergence between mismatched HLA as a driver of clinical tolerability in UD-HCT. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.22.01229","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T21:01:53Z","timestamp":1674248513000},"page":"2416-2427","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":49,"title":["Impact of the HLA Immunopeptidome on Survival of Leukemia Patients After Unrelated Donor Transplantation"],"prefix":"10.1200","volume":"41","author":[{"given":"Pietro","family":"Crivello","sequence":"first","affiliation":[{"name":"Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3696-5803","authenticated-orcid":false,"given":"Esteban","family":"Arrieta-Bola\u00f1os","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, Germany"},{"name":"German Cancer Consortium, partner site Essen\/D\u00fcsseldorf (DKTK), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilun","family":"He","sequence":"additional","affiliation":[{"name":"CIBMTR (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program\/Be The Match, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI"},{"name":"Department of Medicine, Medical College of Wisconsin, CIBMTR (Center for International Blood and Marrow Transplant Research), Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Fingerson","sequence":"additional","affiliation":[{"name":"CIBMTR (Center for 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