{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:23:49Z","timestamp":1792783429153,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004169","name":"Meiji Seika Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004169","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hiroshima University","id":[{"id":"https:\/\/ror.org\/03t78wx29","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immunosuppressants can be used to treat chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplantation. However, real-world retrospective studies on practical regimens and health outcomes remain limited. To identify challenges associated with systemic treatment of cGVHD, we analyzed anonymized Japanese medical insurance claims data. Among 1090 patients with cGVHD, 81% received systemic treatment with immunosuppressive drugs. The most common initial regimen was a combination of tacrolimus and steroids. Second-line treatment was provided in 44% of patients including the addition of steroids, calcineurin inhibitors, or mycophenolate mofetil, or switching to another drug class. Third-line treatment was provided in 23% and steroid monotherapy was the most commonly used. Immunosuppressive treatment was temporarily discontinued in 79% of patients but was re-initiated in approximately a half of them. Young recipients (&lt;\u200915 years) and umbilical cord blood recipients had lower rates of treatment re-initiation and conferred lower mortality. Various complications were observed after transplantation but most of them gradually resolved, with the exception of chronic bone, eye, and respiratory system disorders. The immunocompromised state of these patients was also reflected in the frequent use of anti-infective agents. The adverse effects associated with long-term steroid use pose a clinical challenge, highlighting the need for alternative treatments.<\/jats:p>","DOI":"10.1007\/s12185-026-04228-9","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:34:13Z","timestamp":1779885253000},"page":"580-589","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-world treatments and outcomes of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a Japanese claims analysis"],"prefix":"10.1007","volume":"124","author":[{"given":"Takero","family":"Shindo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Shindo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"4228_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaad.2022.12.024","volume":"90","author":"E Baumrin","year":"2024","unstructured":"Baumrin E, Loren AW, Falk SJ, Mays JW, Cowen EW. Chronic graft-versus-host disease. Part I- epidemiology, pathogenesis, and clinical manifestations. J Am Acad Dermatol. 2024;90:1\u201316.","journal-title":"J Am Acad Dermatol"},{"key":"4228_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1532\/ijh97.03176","volume":"79","author":"PJ Martin","year":"2004","unstructured":"Martin PJ, Carpenter PA, Sanders JE, Flowers ME. Diagnosis and clinical management of chronic graft-versus-host disease. Int J Hematol. 2004;79:221\u20138. https:\/\/doi.org\/10.1532\/ijh97.03176.","journal-title":"Int J Hematol"},{"key":"4228_CR3","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/978-3-030-02278-5_44","volume-title":"The EBMT handbook","author":"D Wolff","year":"2019","unstructured":"Wolff D, Lawitschka A. Chronic graft-versus-host disease. In: The EBMT handbook. Cham: Springer International Publishing; 2019. p. 331\u201345. https:\/\/doi.org\/10.1007\/978-3-030-02278-5_44."},{"key":"4228_CR4","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41409-018-0290-6","volume":"54","author":"E Martelin","year":"2019","unstructured":"Martelin E, Volin L, It\u00e4l\u00e4-Remes M, Niittyvuopio R, Lindstr\u00f6m V, Heiskanen J, et al. Incidence and risk factors of secondary cancers after allogeneic stem cell transplantation: analysis of a single centre cohort with a long follow-up. Bone Marrow Transplant. 2019;54:334\u20137. https:\/\/doi.org\/10.1038\/s41409-018-0290-6.","journal-title":"Bone Marrow Transplant"},{"key":"4228_CR5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/bmt.2011.23","volume":"47","author":"A Yokota","year":"2012","unstructured":"Yokota A, Ozawa S, Masanori T, Akiyama H, Ohshima K, Kanda Y, et al. Secondary solid tumors after allogeneic hematopoietic SCT in Japan. Bone Marrow Transplant. 2012;47:95\u2013100. https:\/\/doi.org\/10.1038\/bmt.2011.23.","journal-title":"Bone Marrow Transplant"},{"key":"4228_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/jgf2.422","volume":"22","author":"K Nagai","year":"2021","unstructured":"Nagai K, Tanaka T, Kodaira N, Kimura S, Takahashi Y, Nakayama T. Data resource profile: JMDC claims database sourced from health insurance societies. J Gen Fam Med. 2021;22:118\u201327. https:\/\/doi.org\/10.1002\/jgf2.422.","journal-title":"J Gen Fam Med"},{"key":"4228_CR7","volume-title":"Goodman and Gilman\u2019s the pharmacological basis of therapeutics","author":"CJ Hupfeld","year":"2022","unstructured":"Hupfeld CJ, I\u00f1iguez-Lluhi JA. Chapter 50 Adrenocorticotropic hormone, adrenal steroids, and the adrenal cortex. In: Brunton LL, Knollmann BC, editors. Goodman and Gilman\u2019s the pharmacological basis of therapeutics. New York: McGraw-Hill; 2022."},{"key":"4228_CR8","doi-asserted-by":"publisher","first-page":"504.e1","DOI":"10.1016\/j.jtct.2020.12.027","volume":"27","author":"CR Bachier","year":"2021","unstructured":"Bachier CR, Aggarwal SK, Hennegan K, Milgroom A, Francis K, Dehipawala S, et al. Epidemiology and treatment of chronic graft-versus-host disease post-allogeneic hematopoietic cell transplantation: a US claims analysis. Transplant Cell Ther. 2021;27:504.e1-504.e6. https:\/\/doi.org\/10.1016\/j.jtct.2020.12.027.","journal-title":"Transplant Cell Ther"},{"key":"4228_CR9","doi-asserted-by":"publisher","first-page":"907.e1","DOI":"10.1016\/j.jtct.2024.06.023","volume":"30","author":"J Kanda","year":"2024","unstructured":"Kanda J, Mitsuyoshi T, Sakurai M, Nishimori H, Murata M, Uchida N, et al. Real-world outcomes of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in Japan: retrospective analysis of the Transplant Registry Unified Management Program registry. Transplant Cell Ther. 2024;30:907.e1-907.e16. https:\/\/doi.org\/10.1016\/j.jtct.2024.06.023.","journal-title":"Transplant Cell Ther"},{"key":"4228_CR10","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/bmt.2013.151","volume":"49","author":"J Kanda","year":"2014","unstructured":"Kanda J, Nakasone H, Atsuta Y, Toubai T, Yokoyama H, Fukuda T, et al. Risk factors and organ involvement of chronic GVHD in Japan. Bone Marrow Transplant. 2014;49:228\u201335. https:\/\/doi.org\/10.1038\/bmt.2013.151.","journal-title":"Bone Marrow Transplant"},{"key":"4228_CR11","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.jtct.2021.03.012","volume":"27","author":"DM Ponce","year":"2021","unstructured":"Ponce DM, Politikos I, Alousi A, Carpenter PA, Milano F, MacMillan ML, et al. Guidelines for the prevention and management of graft-versus-host disease after cord blood transplantation. Transplant Cell Ther. 2021;27:540\u20134. https:\/\/doi.org\/10.1016\/j.jtct.2021.03.012.","journal-title":"Transplant Cell Ther"},{"issue":"Suppl 2","key":"4228_CR12","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.1002\/sctm.20-0495","volume":"10","author":"X Zhu","year":"2021","unstructured":"Zhu X, Tang B, Sun Z. Umbilical cord blood transplantation: still growing and improving. Stem Cells Transl Med. 2021;10(Suppl 2):S62\u201374. https:\/\/doi.org\/10.1002\/sctm.20-0495.","journal-title":"Stem Cells Transl Med"},{"key":"4228_CR13","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-024-03866-1","author":"K Sanda","year":"2024","unstructured":"Sanda K, Fuji S, Tada Y, Shingai Y, Kasahara H, Yuda S, et al. Impact of stem cell source on secondary steroid for chronic GVHD after allogeneic hematopoietic cell transplantation. Int J Hematol. 2024. https:\/\/doi.org\/10.1007\/s12185-024-03866-1.","journal-title":"Int J Hematol"},{"key":"4228_CR14","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1097\/TP.0b013e31826e592e","volume":"95","author":"HA Chakkera","year":"2013","unstructured":"Chakkera HA, Mandarino LJ. Calcineurin inhibition and new-onset diabetes mellitus after transplantation. Transplantation. 2013;95:647\u201352. https:\/\/doi.org\/10.1097\/TP.0b013e31826e592e.","journal-title":"Transplantation"},{"key":"4228_CR15","doi-asserted-by":"crossref","unstructured":"M.H. Jagasia, H.T. Greinix, M. Arora National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease- I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21","DOI":"10.1016\/j.bbmt.2015.02.025"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04228-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-026-04228-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-026-04228-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:59:11Z","timestamp":1791194351000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-026-04228-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["4228"],"URL":"https:\/\/doi.org\/10.1007\/s12185-026-04228-9","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"14 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"T. Shindo received advisory fees from Meiji Seika Pharma Co., Ltd. and lecture fees from Novartis Pharmaceuticals, Johnson and Johnson Innovative Medicine, and Meiji Seika Pharma Co., Ltd. M. Shindo is an employee of Meiji Seika Pharma Co., Ltd., which funded this study.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}