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This single\u2010center study investigates the outcomes of 94 adults with hematological malignancies undergoing MMUD allo\u2010HCT with PTCY and tacrolimus (Tac) (PTCY\u2010Tac) between 2014 and 2023. The median age was 53\u2009years, and 60.6% were male. Peripheral blood stem cells were infused in all cases. By Day +100, the cumulative incidence of Grades II\u2013IV and Grades III and IV acute GVHD were 33.0% and 9.7%, with 2\u2010year incidence of moderate\u2010to\u2010severe chronic GVHD at 12.6%. By Day +30, 40.8% of patients experienced bacterial bloodstream infections, and 52.4% had cytomegalovirus (CMV) reactivation before letermovir prophylaxis. With letermovir's introduction, CMV reactivation rates dropped significantly, with only one case reported. At 3\u2009years, overall survival was 60.8%, non\u2010relapse mortality was 23%, and the cumulative incidence of relapse was 24.5%. HLA Class I or II mismatches did not affect key outcomes or GVHD rates. These findings demonstrate that PTCY\u2010Tac offers effective GVHD prevention and favorable outcomes in MMUD allo\u2010HCT, supporting its application for patients without fully matched donors.<\/jats:p>","DOI":"10.1111\/ejh.14378","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T09:25:22Z","timestamp":1735550722000},"page":"650-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimized <scp>GVHD<\/scp> Prevention in <scp>HLA<\/scp>\u2010Mismatched Unrelated Allogeneic <scp>HCT<\/scp> Using a <scp>PTCY<\/scp>\u2010Based Approach"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-6633","authenticated-orcid":false,"given":"Filipe R.","family":"Pinto","sequence":"first","affiliation":[{"name":"Clinical Hematology Department Unidade Local de Sa\u00fade de Santo Ant\u00f3nio\u2014Hospital de Santo Ant\u00f3nio  Oporto 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