{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:59:34Z","timestamp":1790269174483,"version":"4.1.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["T32HL007622-36"],"award-info":[{"award-number":["T32HL007622-36"]}]},{"name":"National Institutes of Health","award":["1R01CA249211"],"award-info":[{"award-number":["1R01CA249211"]}]},{"name":"National Institutes of Health","award":["UG1HL069330"],"award-info":[{"award-number":["UG1HL069330"]}]},{"name":"National Institutes of Health","award":["1K24HL156896"],"award-info":[{"award-number":["1K24HL156896"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    This prospective, single-arm, multicenter phase 1\/2 trial evaluated vorinostat added to standard graft-versus-host disease (GVHD) prophylaxis in pediatric, adolescent, and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (HCT) from HLA-matched related, HLA-matched unrelated, and haploidentical donors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    Patients aged 3\u201339 years received twice-daily vorinostat with tacrolimus\/methotrexate after HLA-matched HCT from day \u221210 to +30, or with post-transplant cyclophosphamide\/tacrolimus\/mycophenolate mofetil after haploidentical HCT from day +5 to +30. The primary endpoint was cumulative incidence of grade II\u2013IV acute GVHD by day +100. All outcomes were based on intention-to-treat analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Forty-three patients were enrolled; median age was 19 years, with 74% receiving HLA-matched and 26% haploidentical HCT. The recommended phase 2 dose was 60 mg\/m\u00b2 twice daily. No dose-limiting toxicities, unexpected vorinostat-related serious adverse events, or primary graft failures occurred. Median neutrophil and platelet recovery occurred at 14 and 18 days, respectively. Day +100 grade II\u2013IV and III\u2013IV acute GVHD were 14% (95% CI, 5.6, 26) and 4.7% (95% CI, 0.83, 14), respectively. One-year overall survival was 88.4% (95% CI, 79.3, 98.5), relapse 14% (95% CI: 5.6, 26), nonrelapse mortality 4.7% (95% CI: 0.8, 14), and GVHD-free\/relapse-free survival 55.8% (95% CI: 42.8, 72.8). Correlative studies demonstrated on-target HDAC activity, with increased histone acetylation and lower proinflammatory cytokines.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    These findings support randomized evaluation of vorinostat-based GVHD prophylaxis in pediatric and AYA HCT.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRY.<\/jats:bold>\n                    ClinicalTrials.gov, NCT03842696.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.210272","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:28Z","timestamp":1790265628000},"source":"Crossref","is-referenced-by-count":0,"title":["Vorinostat for graft-versus-host disease prevention in pediatric and young adult patients with hematologic malignancies"],"prefix":"10.1172","author":[{"given":"Nicolas","family":"Parnell","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.","family":"Beumer","sequence":"additional","affiliation":[{"name":"Analytical Pharmacology Shared Resource, The Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne","family":"Holleran","sequence":"additional","affiliation":[{"name":"Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Churay","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology\/Blood and, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Rozwadowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Heider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Vander Lugt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L.","family":"Kitko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, Vanderbilt Children\u2019s Hospital, Nashville, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April L.","family":"Rahrig","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Stem Ce, Riley Children\u2019s Health, Indianapolis, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Peres","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology\/Blood and, Henry Ford Health, Detroit, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children\u2019s Healthcare of Atlanta,, Emory University, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-An","family":"Talano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, Medical College of Wisconsin, Milwaukee, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa A.","family":"Fabrizio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, Children\u2019s Hospital Colorado, Aurora, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Abusin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Yanik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Magenau","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Riwes","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus J.","family":"Geer","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Anand","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monalisa","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6323-9623","authenticated-orcid":true,"given":"Attaphol","family":"Pawarode","sequence":"additional","affiliation":[{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Votruba","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neuropsychology Program, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7264-8429","authenticated-orcid":true,"given":"Pavan","family":"Reddy","sequence":"additional","affiliation":[{"name":"Dan L. Duncan Comprehensive Cancer Center, Houston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-3834","authenticated-orcid":true,"given":"Sung Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology\/Blood a, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,24]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/210272\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:28Z","timestamp":1790265628000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/210272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.210272"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.210272","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}