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A novel scoring system for ranking HLA mismatches for these donors was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010resolution HLA types were used to determine amino acid mismatches located in the HLA antigen\u2010recognition domain. The location and physicochemical properties of mismatched amino acids were used to assign scores for peptide binding, T\u2010cell receptor docking, and HLA structure\/function. The scores were tested using a cohort of 2319 patients with leukemia or myelodysplastic syndrome who received their first unrelated donor transplant using conventional graft\u2010versus\u2010host disease (GVHD) prophylaxis between 2000 and 2014. Donors were 7\/8 HLA\u2010matched with a single HLA Class I mismatch. Primary outcomes were overall survival and acute GVHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The scores did not significantly (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01) associate with transplant outcomes, although a Peptide Score = 0 (i.e., no differences in peptide binding; <jats:italic>N<\/jats:italic>\u00a0=\u00a0146, 6.3%) appears to have lower transplant\u2010related mortality (TRM) compared to higher scores (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.019). HLA mismatches with Peptide Score\u00a0=\u00a00 were predominately HLA\u2010C*03:03\/03:04 (62%), previously reported to be a permissive mismatch, and a group of 28 other HLA mismatches (38%) that showed similar associations with TRM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that HLA mismatches that do not alter peptide binding or orientation (Peptide Score\u00a0=\u00a00) could expand the number of permissive HLA mismatches. Further investigation is needed to confirm this observation and to explore alternative scoring systems for ranking HLA mismatched donors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ctr.15478","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T08:43:58Z","timestamp":1731055438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6706-0273","authenticated-orcid":false,"given":"Lee Ann","family":"Baxter\u2010Lowe","sequence":"first","affiliation":[{"name":"University of Southern California and Children's Hospital Los Angeles  Los Angeles California 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