{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:16:25Z","timestamp":1784200585148,"version":"3.55.0"},"reference-count":71,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for many malignant and non-malignant hematologic disorders. Chronic graft-versus-host (cGVHD) disease remains a significant hurdle for long-term survival in patients post allo-HCT, and it remains the leading cause of late non-relapse mortality. The risk factors for development of cGVHD include degree of human leukocyte antigen (HLA) disparity, increasing recipient age, use of peripheral blood stem cells as a source, myeloablative conditioning regimens, prior acute GVHD (aGVHD), and female donor to male recipient. Our biological understanding of cGVHD is mostly derived from transplantation mouse models and patient data. There are three distinct phases in the development of cGVHD. Approaches to prevent GVHD include pharmacologic strategies such as calcineurin inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil). Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy for GVCHD prevention especially in a setting of reduced intensity conditioning. Other approaches include serotherapy (ATG, Campath) and graft manipulation strategies. A significant obstacle to evaluating the response of novel GVHD-directed therapies has been standardized response assessments. This has functioned as a barrier to designing and interpreting clinical trials that are structured around the treatment of cGVHD. Novel endpoints including failure-free survival, Graft-versus-host disease-free, relapse-free survival (GRFS), and current GVHD-free, relapse-free survival (CGRFS) may create a clearer picture for post-HCT outcomes. Targeted therapies including Bruton's tyrosine kinase inhibition, JAK1\/2 inhibition, and ROCK2 inhibitors have improved cGVHD therapy, especially in the steroid refractory setting. Continued improvement in prophylactic strategies for cGVHD, identification of accurate cGVHD treatment endpoints, and access to novel therapeutic agents are expected to improve cGVHD outcomes.<\/jats:p>","DOI":"10.1182\/hematology.2023000427","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T15:07:37Z","timestamp":1702048057000},"page":"164-170","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Chronic GVHD: review advances in prevention, novel endpoints, and targeted strategies"],"prefix":"10.1182","volume":"2023","author":[{"given":"Idoroenyi","family":"Amanam","sequence":"first","affiliation":[{"name":"City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Otoukesh","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monzr M.","family":"Al Malki","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep","family":"Salhotra","sequence":"additional","affiliation":[{"name":"City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"issue":"4","key":"2023120815052601700_hem2023000427C1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1586\/ehm.10.32","article-title":"Relapse after allogeneic stem cell transplantation","volume":"3","author":"Barrett","year":"2010","journal-title":"Expert Rev Hematol"},{"issue":"5","key":"2023120815052601700_hem2023000427C2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/03007995.2021.1893676","article-title":"Healthcare resource utilization and costs among patients with steroid-resistant chronic graft-versus-host disease in the United States: a retrospective claims database analysis","volume":"37","author":"Yu","year":"2021","journal-title":"Curr Med Res Opin"},{"issue":"17","key":"2023120815052601700_hem2023000427C3","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1182\/blood-2010-11-319509","article-title":"Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium","volume":"117","author":"Pidala","year":"2011","journal-title":"Blood"},{"issue":"2","key":"2023120815052601700_hem2023000427C4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bbmt.2014.10.021","article-title":"Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research","volume":"21","author":"Arai","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"issue":"1","key":"2023120815052601700_hem2023000427C5","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1182\/hematology.2021000257","article-title":"Allogeneic hematopoietic cell transplantation for older patients","volume":"2021","author":"Lin","year":"2021","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"6","key":"2023120815052601700_hem2023000427C6","doi-asserted-by":"crossref","first-page":"504.e1","DOI":"10.1016\/j.jtct.2020.12.027","article-title":"Epidemiology and treatment of chronic graft-versus-host disease post-allogeneic hematopoietic cell transplantation: a US claims analysis","volume":"27","author":"Bachier","year":"2021","journal-title":"Transplant Cell Ther"},{"issue":"26","key":"2023120815052601700_hem2023000427C7","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1056\/NEJMra1703472","article-title":"Pathophysiology of chronic graft-versus-host disease and therapeutic targets","volume":"377","author":"Zeiser","year":"2017","journal-title":"N Engl J Med"},{"issue":"3","key":"2023120815052601700_hem2023000427C8","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","article-title":"National Institutes of Health consensus development project on criteria for clinical trials in chronic graft- versus-host disease: I. 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