{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:46:13Z","timestamp":1787499973499,"version":"build-2736575974"},"reference-count":69,"publisher":"American Society of Hematology","issue":"16","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P\u00a0=\u00a0.0002), as well as any grade (P = .003) and moderate-severe (P &amp;lt; .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P\u00a0=\u00a0.003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted na\u00efve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to na\u00efve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/bloodadvances.2023010973","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T13:58:57Z","timestamp":1714139937000},"page":"4294-4310","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["High-dose alemtuzumab and cyclosporine vs tacrolimus, methotrexate, and sirolimus for chronic graft-versus-host disease prevention"],"prefix":"10.1182","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-1109","authenticated-orcid":false,"given":"Noa G.","family":"Holtzman","sequence":"first","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Curtis","sequence":"additional","affiliation":[{"name":"2Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"3Ascension Maryland Saint Agnes Hospital, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel B.","family":"Salit","sequence":"additional","affiliation":[{"name":"2Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"2Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"5Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-0211","authenticated-orcid":false,"given":"Filip","family":"Pirsl","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-2176","authenticated-orcid":false,"given":"Alen","family":"Ostojic","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"6Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, 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