{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:33:59Z","timestamp":1790393639236,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"33","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,11,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>To determine whether sirolimus (SIR) and cyclosporine (CSP) combined with post-transplantation cyclophosphamide (PTCy), after nonmyeloablative or reduced-intensity conditioning unrelated donor hematopoietic cell transplantation (HCT), would be more effective than SIR, CSP, and mycophenolate mofetil (MMF) in reducing the risk of chronic graft-versus-host disease (cGVHD) without increasing risk of recurrent malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In a Phase II trial of HLA-matched or mismatched unrelated donor mobilized blood HCT (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03246906\">NCT03246906<\/jats:ext-link>\n                      ), adults with hematologic malignancies ineligible for myeloablative HCT were randomly assigned 1:1 to GVHD prophylaxis with SIR\/CSP\/PTCy (50 mg\/kg once daily on days +3, +4) or SIR\/CSP\/MMF. The primary end point was 1-year chronic GVHD-free relapse-free survival (CRFS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      One hundred forty-five patients were randomly assigned and transplanted. Median follow-up among survivors was 3.0 (range, 0.6-7.0) years. Comparing PTCy-based with non\u2013PTCy-based immunosuppression, estimated 1-year CRFS was 73% (95% CI, 61% to 82%) versus 48% (95% CI, 36% to 59%), translating into a hazard ratio (HR) for CRFS failure of 0.46 (95% CI, 0.26 to 0.79;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .005) for PTCy. Probabilities of acute GVHD (aGVHD) grades II-IV and III-IV, respectively, were 40% versus 42% and 6% versus 10%. One-year estimates for secondary end points were as follows: moderate-to-severe cGVHD, 3% (95% CI, 1% to 9%) versus 33% (95% CI, 22% to 44%); relapse, 15% versus 15%; progression-free survival, 75% versus 78%; survival, 86% versus 86%; and nonrelapse mortality, 10% versus 7%. The HR of \u2265grade 3 infections with PTCy versus non-PTCy was 2.65 (95% CI, 1.41 to 4.97;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>After HLA-matched or mismatched unrelated donor mobilized blood HCT, replacing MMF with PTCy, when used in combination with SIR and CSP, significantly reduced risk of cGVHD, without increasing risks of aGVHD or relapse. Thus, the combination of PTCy and SIR\/CSP may have synergistic cGVHD-protective effects warranting further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01238","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T19:59:07Z","timestamp":1759521547000},"page":"3600-3609","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-1976","authenticated-orcid":true,"given":"Masumi","family":"Ueda Oshima","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Department of Medicine, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0823-0244","authenticated-orcid":true,"given":"Phuong T.","family":"Vo","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Department of Medicine, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Boeckh","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Bouvier","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-0714","authenticated-orcid":true,"given":"Paul A.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5680-8688","authenticated-orcid":true,"given":"Marco","family":"Mielcarek","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Department of Medicine, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6454-3683","authenticated-orcid":true,"given":"Effie W.","family":"Petersdorf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA"},{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Storb","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Department of Medicine, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Gooley","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9767-9739","authenticated-orcid":true,"given":"Brenda 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