{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:05:32Z","timestamp":1784563532421,"version":"3.55.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi260654-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Relapse limits survival after allogeneic hematopoietic cell transplant. Although human leukocyte antigen\u2013matched related donors (MRDs) are traditionally preferred, mismatched unrelated donors (MMUDs) using posttransplant cyclophosphamide may provide stronger graft-vs-leukemia effects, potentially altering donor selection strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare outcomes between MRD and MMUD transplant in the posttransplant cyclophosphamide era and assess whether MMUD grafts are associated with lower relapse rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This retrospective cohort study (January 1, 2017, to August 31, 2024) assessed 1038 patients with acute leukemia or myelodysplastic syndromes and\/or myeloproliferative neoplasms undergoing their first peripheral blood hematopoietic cell transplant using posttransplant cyclophosphamide. The MRD cohort was from a single tertiary center, and the MMUD cohort was from the Center for International Blood and Marrow Transplant Research. Data were analyzed between January 19, 2026, and April 2, 2026.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>Transplant from MRD (n\u2009=\u2009306) vs MMUD (n\u2009=\u2009732).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Disease-free survival (DFS), overall survival (OS), relapse, nonrelapse mortality, and graft-vs-host disease (GVHD). The study used inverse probability of treatment weighting with overlap weights and bootstrapping to address structural confounding, particularly donor age. Cox proportional hazard models were used to compare outcomes between groups and confirm that phrasing with the author.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1038 patients (526 [50.7%] female), donors in the MRD group were older (median [IQR] age, 57 [45-64] years) than in the MMUD group (median [IQR] age, 28 [24-35] years) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Recipient age was similar (median [IQR] age, 60 [47-66] vs 58 [47-65] years;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.40). In patients with a high or very high Disease Risk Index (DRI), MMUD transplant was associated with significantly lower relapse hazard vs MRD (weighted hazard ratio [HR], 0.56; 95% CI, 0.33-0.94;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.03), although DFS (HR, 0.71; 95% CI, 0.46-1.11;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.14) and OS (HR, 0.85; 95% CI, 0.53-1.37;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.51) were similar. Conversely, in patients with low to intermediate DRIs, hazard estimates for DFS (HR, 1.24; 95% CI, 0.92-1.66;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.16) and OS (HR, 1.36; 95% CI, 0.99-1.88;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.06) lacked precision. MMUD was associated with lower risk of grade III to IV acute GVHD (HR, 0.56; 95% CI, 0.32-0.98;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.04) but higher chronic GVHD (HR, 2.82; 95% CI, 2.02-3.95;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-zoi260654-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this cohort study, MMUD transplant was associated with lower relapse rates compared with MRD in patients with high-risk malignant tumors, potentially reflecting enhanced alloreactivity, although accompanied by increased chronic GVHD. These findings indicated that the immunologic role of human leukocyte antigen mismatch varies by disease risk, suggesting that MMUD grafts offered a distinct risk-benefit profile that warrants further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.23265","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:30:31Z","timestamp":1784561431000},"page":"e2623265","source":"Crossref","is-referenced-by-count":0,"title":["Mismatched Unrelated vs Matched Related Donor Transplant With Posttransplant Cyclophosphamide Among Patients With Blood Cancers"],"prefix":"10.1001","volume":"9","author":[{"given":"Rohtesh S.","family":"Mehta","sequence":"first","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra 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Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Oran","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday","family":"Popat","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Champlin","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Transplantation and Cellular Therapy, The 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