{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:08:39Z","timestamp":1791526119085,"version":"4.3.4"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>For patients with hematologic malignancies, relapse is the leading cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Frequently, relapses are explained by immune evasion through alterations of human leukocyte antigens (HLAs), but determinants and clinical consequences remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed 533 relapses of hematologic cancers after allo-HCT from different donor types, conducted at 27 centers worldwide. Genomic loss of mismatched HLA (HLA loss) was assessed using a newly developed next-generation sequencing pipeline. Clinical and immunogenetic factors associated with HLA loss were evaluated. Using HLA data from approximately 5 million individuals, a web-based tool to infer HLA incompatibility phasing was developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      HLA loss occurred in 15.6% of relapses, with significant variation according to donor type (28.7% haploidentical family, 7.2% unrelated adult, 2.7% cord blood,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). The distribution of HLA mismatches across the patient's haplotypes, predicted through the phasing tool, was strongly associated with HLA loss, with an incidence of 27.6% when HLA mismatches were in the same haplotype, compared with 5.4% if present on different haplotypes (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). HLA loss affected postrelapse outcomes, abrogating the efficacy of original donor lymphocyte infusions, with significant survival advantage by second allo-HCT from a different donor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The likelihood of HLA loss varies significantly according to the number and positioning of HLA mismatches between patient and donor. A newly developed phasing tool enables reliable prediction of its risk, supporting informed donor selection. Routine assessment of HLA loss at relapse is warranted, as it critically affects the success of immunologic salvage therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00113","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T19:59:14Z","timestamp":1782417554000},"page":"2221-2232","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Donor Selection and Human Leukocyte Antigen Loss Leukemia Relapse After Hematopoietic Cell Transplantation"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5827-8000","authenticated-orcid":false,"given":"Katharina","family":"Fleischhauer","sequence":"first","affiliation":[{"name":"Experimental Cellular Therapy, University Hospital Essen, Essen, Germany"},{"name":"German Cancer Consortium, Partner Site Essen\/D\u00fcsseldorf, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-3057","authenticated-orcid":false,"given":"Cristina","family":"Toffalori","sequence":"additional","affiliation":[{"name":"Unit of Immunogenetics, Leukemia Genomics and Immunobiology, I.R.C.C.S. San Raffaele Scientific Institute, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-569X","authenticated-orcid":false,"given":"Federica","family":"Cugnata","sequence":"additional","affiliation":[{"name":"University Centre for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"DKMS Group, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0175-9093","authenticated-orcid":false,"given":"Giorgio","family":"Orofino","sequence":"additional","affiliation":[{"name":"Unit of Immunogenetics, Leukemia Genomics and Immunobiology, I.R.C.C.S. San Raffaele Scientific Institute, Milano, Italy"},{"name":"Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. 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San Raffaele Scientific Institute, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcberra","family":"Ahci-Hanci","sequence":"additional","affiliation":[{"name":"Experimental Cellular Therapy, University Hospital Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-9573","authenticated-orcid":false,"given":"Vinzenz","family":"Lange","sequence":"additional","affiliation":[{"name":"DKMS Life Science Lab, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-9606","authenticated-orcid":false,"given":"Carlheinz R.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Zentrales Knochenmarkspender-Register Deutschland (ZKRD), Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-5308","authenticated-orcid":false,"given":"Desiree","family":"Kunadt","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital Dresden, TU Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-3029","authenticated-orcid":false,"given":"Martin","family":"Bornh\u00e4user","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital Dresden, TU Dresden, Dresden, Germany"},{"name":"National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany"},{"name":"German Cancer Research Center (DKFZ), Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2767-8191","authenticated-orcid":false,"given":"Guillermo","family":"Sanz","sequence":"additional","affiliation":[{"name":"Hospital Universitari i Polit\u00e8cnic La Fe, Valencia, Spain"},{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, Valencia, Spain"},{"name":"The Departament de Medicina Universitat de Valencia, CIBERONC, Instituto Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5810-1192","authenticated-orcid":false,"given":"Robert","family":"Soiffer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Waterhouse","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Giaccone","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Transplant and Cell Therapy Unit, University of Torino, A.O.U. 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