{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:12:44Z","timestamp":1793646764726,"version":"4.5.1"},"reference-count":20,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,21]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. Although high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1\/2 trial evaluating high-dose palifermin for preventing severe chronic GVHD (CGVHD) in matched unrelated donor T-cell replete peripheral blood HCT after reduced-intensity conditioning (RIC). Using a 3+3 design, we determined the recommended phase 2 dose (RP2D), followed by an expansion phase. Palifermin (180-720 \u03bcg\/kg) was given on day \u22127 before HCT. All 31 patients received fludarabine\/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. Palifermin was well tolerated, with self-limiting rash and pancreatic enzyme elevations as notable grade 3\/4 adverse events. The RP2D was 720 \u03bcg\/kg. Remarkably, no patients at this dose developed grade 2 to 4 acute GVHD (AGVHD [0\/19]), although severe CGVHD rates (primary end point) remained unchanged compared to historical controls. Posttransplant lymphocyte phenotyping suggests palifermin modulates regulatory and na\u00efve CD4+ T-cell numbers. These findings indicate that high-dose palifermin with RIC is safe and may prevent AGVHD, although it did not affect CGVHD rates in this study. This trial was registered at www.ClinicalTrials.gov as #NCT02356159.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024028303","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T09:48:16Z","timestamp":1746611296000},"page":"944-950","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":7,"title":["Phase 1\/2 study of high-dose palifermin for GVHD prophylaxis in patients undergoing HLA-matched unrelated donor HCT"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-4592","authenticated-orcid":false,"given":"Eduard","family":"Schulz","sequence":"first","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"2Myeloid Malignancies Program, Center for Cancer Research, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Curtis","sequence":"additional","affiliation":[{"name":"3Mount Auburn Hematology Associates, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa G.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"4Sylvester Comprehensive Cancer Center, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"5Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3693-0559","authenticated-orcid":false,"given":"Kaska","family":"Wloka","sequence":"additional","affiliation":[{"name":"6Laboratory of Pathology, Center for Cancer Research, 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, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Mina","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"},{"name":"2Myeloid Malignancies Program, Center for Cancer Research, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najla","family":"El Jurdi","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"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, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Carpenter","sequence":"additional","affiliation":[{"name":"1Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahshid","family":"Golagha","sequence":"additional","affiliation":[{"name":"7Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene","family":"Sirajuddin","sequence":"additional","affiliation":[{"name":"8Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2643-6289","authenticated-orcid":false,"given":"Theo","family":"Heller","sequence":"additional","affiliation":[{"name":"9Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"10Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances T.","family":"Hakim","sequence":"additional","affiliation":[{"name":"11Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Rubin","sequence":"additional","affiliation":[{"name":"12Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald E.","family":"Gress","sequence":"additional","affiliation":[{"name":"11Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, 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