{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:07:04Z","timestamp":1788502024345,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG FL 843\/1\u20101"],"award-info":[{"award-number":["DFG FL 843\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR\u20102011\u201002350175"],"award-info":[{"award-number":["GR\u20102011\u201002350175"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric\/young adults patients, treated for malignant disorders with HSCT from 9\u201310\/10 HLA\u2010matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA\u2010A, \u2010B, \u2010C, \u2010DRB1, \u2010DQB1 and \u2010DPB1, using the locus median to stratify patients with \u2018high\u2019 or \u2018low\u2019 HED. Patients with high HED\u2010B and \u2010DRB1 showed significantly improved disease\u2010free survival (DFS), especially when combined (70.8% vs 53.7% <jats:italic>p<\/jats:italic>\u00a0=\u00a00.008). High HED\u2010B\u2009+\u2009\u2010DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% <jats:italic>p<\/jats:italic>\u00a0=\u00a00.014), and concomitant reduction of non\u2010relapse\u2010mortality (5.1% vs 21.1% <jats:italic>p<\/jats:italic>\u00a0=\u00a00.006). The impact on OS and DFS of combined HED\u2010B\u2009+\u2009\u2010DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.009; and HR 0.45, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.007 respectively]. Only high HED scores for HLA\u2010DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.<\/jats:p>","DOI":"10.1111\/bjh.18561","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T06:15:56Z","timestamp":1668665756000},"page":"622-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Human leukocyte antigen evolutionary divergence influences outcomes of paediatric patients and young adults affected by malignant disorders given allogeneic haematopoietic stem cell transplantation from unrelated donors"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-4046","authenticated-orcid":false,"given":"Pietro","family":"Merli","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-5013","authenticated-orcid":false,"given":"Pietro","family":"Crivello","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cellular Therapy University Hospital Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-0857","authenticated-orcid":false,"given":"Luisa","family":"Strocchio","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita Maria","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome 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Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-0836","authenticated-orcid":false,"given":"Stefania","family":"Gaspari","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Galaverna","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy IRCCS Bambino Ges\u00f9 Children's Hospital  Rome 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