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Advances in the understanding of allogeneic HCT biology and immunology have paved the way for novel clinical approaches to GVHD prophylaxis, highlighted by the broad adoption of posttransplant cyclophosphamide and the approval of abatacept by the US Food and Drug Administration to prevent acute GVHD. Patients undergoing allogeneic HCT are now experiencing severe acute GVHD at historically low rates, and significant improvements in preventing chronic GVHD are also being achieved. This review highlights key pharmacological approaches and graft manipulation strategies being used or investigated for GVHD prophylaxis. Furthermore, we discuss the ongoing unmet needs in GVHD prevention and the challenges in addressing these areas in future clinical trials.<\/jats:p>","DOI":"10.1002\/ajh.27597","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T23:55:06Z","timestamp":1742860506000},"page":"30-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Update in GVHD Prophylaxis: Novel Pharmacologic and Graft Manipulation Strategies"],"prefix":"10.1002","volume":"100","author":[{"given":"Elizabeth O.","family":"Hexner","sequence":"first","affiliation":[{"name":"Center for Cellular Immunotherapies and Abramson Cancer Center University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-8974","authenticated-orcid":false,"given":"Zachariah","family":"DeFilipp","sequence":"additional","affiliation":[{"name":"Hematopoietic Cell Transplant and Cellular Therapy Program Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703472"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-514786"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004941"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03643"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2022.09.013"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation.V2012.1.251.3798879"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.245688"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-567164"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00636"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2002.v8.pm12171484"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.03.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-344853"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007535"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2021.06.011"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.04.012"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000487"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-024-01032-8"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00184"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03502"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30221-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2215943"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005847"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02293"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.06.008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02225-7"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-193827"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2021.02.011"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004846"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.12.021"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003779"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010545"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2024.08.015"},{"issue":"12","key":"e_1_2_10_35_1","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1182\/blood.V83.12.3815.3815","article-title":"In Vivo Blockade of CD28\/CTLA4: B7\/BB1 Interaction With CTLA4\u2010Ig Reduces Lethal Murine Graft\u2010Versus\u2010Host Disease Across the Major Histocompatibility Complex Barrier in Mice","volume":"83","author":"Blazar B. 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