{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:09:28Z","timestamp":1793725768472,"version":"4.6.1"},"reference-count":178,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute graft-versus-host disease (GVHD) is 1 of the major life-threating complications after allogeneic cell transplantation. Although steroids remain first-line treatment, roughly one-half of patients will develop steroid-refractory GVHD (SR-GVHD), which portends an extremely poor prognosis. Many agents that have shown encouraging response rates in early phase 1\/2 trials for prevention and treatment have been unsuccessful in demonstrating a survival advantage when applied in the setting of SR-GVHD. The discovery of novel treatments has been further complicated by the absence of clinically informative animal models that address what may reflect a distinct pathophysiology. Nonetheless, the combined knowledge of established bone marrow transplantation models and recent human trials in SR-GVHD patients are beginning to illuminate novel mechanisms for inhibiting T-cell signaling and promoting tissue tolerance that provide an increased understanding of the underlying biology of SR-GVHD. Here, we discuss recent findings of newly appreciated cellular and molecular mechanisms and provide novel translational opportunities for advancing the effectiveness of treatment in SR-GVHD.<\/jats:p>","DOI":"10.1182\/blood.2019000953","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T20:48:54Z","timestamp":1591908534000},"page":"429-440","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":69,"title":["Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-7543","authenticated-orcid":false,"given":"Tomomi","family":"Toubai","sequence":"first","affiliation":[{"name":"Division of Hematology and Cell Therapy, Department of Internal Medicine III, Faculty of Medicine, Yamagata University, Yamagata, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Magenau","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, University Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"1","key":"2020072311262496000_B1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1182\/blood-2011-06-364265","article-title":"Risk factors for acute GVHD and survival after hematopoietic cell transplantation","volume":"119","author":"Jagasia","year":"2012","journal-title":"Blood"},{"issue":"7","key":"2020072311262496000_B2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1053\/bbmt.2002.v8.pm12171485","article-title":"Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems","volume":"8","author":"MacMillan","year":"2002","journal-title":"Biol Blood 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