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Optimizing graft\u2010versus\u2010host disease (GvHD) prophylaxis in this population remains critical to improving outcomes. We performed a retrospective analysis of YAs undergoing unrelated donor HSCT using a contemporary Center for International Blood and Marrow Transplant Research (CIBMTR) dataset. GvHD\u2010free, relapse\u2010free survival (GRFS) at 24\u2009months was evaluated across three GvHD prophylaxis strategies: Group A (post\u2010transplant cyclophosphamide [PTCy]\u2009+\u2009calcineurin inhibitor [CNI]\u2009+\u2009mycophenolate mofetil [MMF]), Group B (CNI\u2009+\u2009methotrexate [MTX]\/MMF), and Group C (CNI\u2009+\u2009MTX\/MMF\u2009+\u2009anti\u2010thymocyte globulin [ATG]). A propensity score\u2010matched (PSM) analysis was conducted to adjust for baseline differences. A total of 1387 YA patients were included. In the total cohort, 24\u2010month GRFS was 58.9% (confidence intervals [95% CI], 53\u201364) in Group A, 32.2% (95% CI, 29\u201336) in Group B and 44.2% (95% CI, 39\u201349) in Group C (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). On multivariable analysis (MVA), both Group A (hazard ratio [HR]\u2009=\u20090.44; 95% CI, 0.35\u20130.54) and Group C (HR\u2009=\u20090.79; 95% CI, 0.70\u20130.90) showed improved GRFS compared to Group B. In the propensity score\u2010matched cohort, GRFS at 24\u2009months remained higher in the PTCy group (58.2%, 95% CI, 52\u201364) versus the CNI\u2010MTX\/MMF\u2009\u00b1\u2009ATG group (32.9%, 95% CI, 27\u201339;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), with PTCy independently associated with improved GRFS (HR\u2009=\u20090.48; 95% CI, 0.40\u20130.60;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). PTCy\u2010based prophylaxis also reduced non\u2010relapse mortality (NRM), with no significant differences in relapse or overall survival (OS) between groups. In this large, retrospective analysis, PTCy was associated with significantly improved GRFS and reduced NRM in YAs undergoing unrelated donor HSCT. These findings support the use of PTCy\u2010based regimens in this population and warrant prospective evaluation.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70269","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T08:15:32Z","timestamp":1764922532000},"page":"630-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of graft\u2010versus\u2010host disease prophylaxis strategies on\n                    <scp>GvHD<\/scp>\n                    \u2010free\/relapse\u2010free survival in young adults undergoing unrelated donor allogeneic haematopoietic cell transplantation: A\u00a0propensity score\u2010matched analysis"],"prefix":"10.1111","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-3245","authenticated-orcid":false,"given":"Nihar","family":"Desai","sequence":"first","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio Rodriguez","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-4626","authenticated-orcid":false,"given":"Eshrak","family":"Al\u2010Shaibani","sequence":"additional","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-4678","authenticated-orcid":false,"given":"Tommy Alfaro","family":"Moya","sequence":"additional","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Novitzky\u2010Basso","sequence":"additional","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun Datt","family":"Law","sequence":"additional","affiliation":[{"name":"Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario 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