{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T18:50:20Z","timestamp":1794336620399,"version":"4.9.0"},"reference-count":31,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>To prevent graft-versus-host disease (GVHD) in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), a calcineurin inhibitor plus methotrexate is routinely used. Early phase studies suggested improved outcomes with Orca-T, an allogeneic T-cell immunotherapy that uses purified donor regulatory T cells to prevent GVHD with significantly less immunosuppression. This phase 3 trial randomized adult patients (N = 187) with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning to receive either Orca-T with tacrolimus or a conventional allograft with tacrolimus and methotrexate (Tac\/MTX), using granulocyte colony-stimulating factor\u2013mobilized peripheral blood from HLA-matched donors. The primary end point was survival free from moderate-to-severe chronic GVHD (cGVHD; cGFS). Using a stratified log-rank test, cGFS was significantly higher in the Orca-T arm than in Tac\/MTX (hazard ratio, 0.26; 95% confidence interval, 0.14-0.47; P&amp;lt; .001). One-year estimates were as follows: cGFS was 78.0% with Orca-T vs 38.4% with Tac\/MTX; cumulative incidence of moderate-to-severe cGVHD was 12.6% with Orca-T and 44.0% with Tac\/MTX (Gray test P&amp;lt; .001); overall survival was 93.9% with Orca-T vs 83.1% with Tac\/MTX (P = .12); GVHD-free and relapse-free survival was 63.1% and 30.9% in the Orca-T and Tac\/MTX arms (P&amp;lt; .001), respectively; nonrelapse mortality (NRM) was 3.4% with Orca-T vs 13.2% with Tac\/MTX (P = .03). Orca-T met the primary end point of improved survival free from cGVHD compared with Tac\/MTX prophylaxis and should be considered a new therapeutic option with low toxicity for GVHD prophylaxis. Moreover, significantly less toxicity was observed with Orca-T patients, including fewer serious infectious complications and less NRM. This trial was registered at www.clinicaltrials.gov as NCT05316701.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025031313","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T17:13:00Z","timestamp":1765559580000},"page":"1168-1177","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":36,"title":["Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial"],"prefix":"10.1182","volume":"147","author":[{"given":"Everett H.","family":"Meyer","sequence":"first","affiliation":[{"name":"1Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep","family":"Salhotra","sequence":"additional","affiliation":[{"name":"2Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita P.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"3Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Pantin","sequence":"additional","affiliation":[{"name":"4Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, HCA Healthcare, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-3615","authenticated-orcid":false,"given":"Sagar S.","family":"Patel","sequence":"additional","affiliation":[{"name":"5Transplant and Cellular Therapy Program, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus T.","family":"Hoeg","sequence":"additional","affiliation":[{"name":"6Division of Malignant Hematology\/Cellular Therapy and Transplantation, Comprehensive Cancer Center, University of California, Davis, Sacramento, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0897-3790","authenticated-orcid":false,"given":"Alexandra","family":"Gomez-Arteaga","sequence":"additional","affiliation":[{"name":"7Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-781X","authenticated-orcid":false,"given":"Rawan","family":"Faramand","sequence":"additional","affiliation":[{"name":"8Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Tamari","sequence":"additional","affiliation":[{"name":"9Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0816-6729","authenticated-orcid":false,"given":"Edmund K.","family":"Waller","sequence":"additional","affiliation":[{"name":"10Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute of Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyajit","family":"Kosuri","sequence":"additional","affiliation":[{"name":"11Division of Hematology and Oncology, University of Chicago Medicine, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-6836","authenticated-orcid":false,"given":"Antonio M.","family":"Jimenez Jimenez","sequence":"additional","affiliation":[{"name":"12Division of Transplantation and Cell Therapy, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1425-7002","authenticated-orcid":false,"given":"Jennifer","family":"Holter-Chakrabarty","sequence":"additional","affiliation":[{"name":"13Transplant & Cellular Therapy Clinic, OU Health Stephenson Cancer Center, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-3655","authenticated-orcid":false,"given":"Bhagirathbhai","family":"Dholaria","sequence":"additional","affiliation":[{"name":"14Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-1058","authenticated-orcid":false,"given":"Yi-Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"15Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1252-6539","authenticated-orcid":false,"given":"Betty K.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"16Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Magenau","sequence":"additional","affiliation":[{"name":"17Blood and Marrow Transplantation Program, Rogel Cancer Center, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Eghtedar","sequence":"additional","affiliation":[{"name":"18Colorado Blood Cancer Institute, HCA HealthONE Presbyterian St. Luke's, Denver, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Murray","sequence":"additional","affiliation":[{"name":"19Orca Bio, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5533-5700","authenticated-orcid":false,"given":"Anna","family":"Pavlova","sequence":"additional","affiliation":[{"name":"19Orca Bio, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-9653","authenticated-orcid":false,"given":"Nathaniel B.","family":"Fernhoff","sequence":"additional","affiliation":[{"name":"19Orca Bio, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Scott","family":"McClellan","sequence":"additional","affiliation":[{"name":"19Orca Bio, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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