{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:16:39Z","timestamp":1788318999007,"version":"build-2803163510"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":60,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Kyowa Kirin Co., Ltd."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"DOI":"10.1007\/s00277-026-07062-5","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:46:54Z","timestamp":1780292814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term safety and effectiveness of romiplostim in patients with refractory aplastic anemia: a nationwide, all-case, post-marketing surveillance study in Japan"],"prefix":"10.1007","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7549-4911","authenticated-orcid":false,"given":"Mitsuhiro","family":"Itagaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kuwazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moe","family":"Matsuura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-3093","authenticated-orcid":false,"given":"Naoshi","family":"Obara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"7062_CR1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1080\/17474086.2017.1302797","volume":"10","author":"S Kojima","year":"2017","unstructured":"Kojima S (2017) Why is the incidence of aplastic anemia higher in Asia? Expert Rev Hematol 10:277\u2013279. https:\/\/doi.org\/10.1080\/17474086.2017.1302797","journal-title":"Expert Rev Hematol"},{"key":"7062_CR2","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3324\/haematol.12855","volume":"93","author":"NS Young","year":"2008","unstructured":"Young NS, Kaufman DW (2008) The epidemiology of acquired aplastic anemia. Haematologica 93:489\u2013492. https:\/\/doi.org\/10.3324\/haematol.12855","journal-title":"Haematologica"},{"key":"7062_CR3","unstructured":"Nakao S, the Guideline Working Group for Revision (2011) Clinical guidelines for aplastic anemia, revised in 2010 [in Japanese]"},{"key":"7062_CR4","unstructured":"Yamazaki H, the Guideline Working Group for Revision (2023) Clinical guidelines for aplastic anemia, revised in 2022 [in Japanese]. https:\/\/zoketsushogaihan.umin.jp\/file\/2022\/AA_final20230801.pdf. Accessed 9 February 2026"},{"key":"7062_CR5","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1007\/s12185-017-2179-3","volume":"105","author":"J Hayakawa","year":"2017","unstructured":"Hayakawa J, Kanda J, Akahoshi Y et al (2017) Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia. Int J Hematol 105:578\u2013586. https:\/\/doi.org\/10.1007\/s12185-017-2179-3","journal-title":"Int J Hematol"},{"key":"7062_CR6","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0037-1963(00)90033-7","volume":"37","author":"G Soci\u00e9","year":"2000","unstructured":"Soci\u00e9 G, Rosenfeld S, Frickhofen N, Gluckman E, Tichelli A (2000) Late clonal diseases of treated aplastic anemia. Semin Hematol 37:91\u2013101. https:\/\/doi.org\/10.1016\/S0037-1963(00)90033-7","journal-title":"Semin Hematol"},{"key":"7062_CR7","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1056\/NEJM199310143291603","volume":"329","author":"G Soci\u00e9","year":"1993","unstructured":"Soci\u00e9 G, Henry-Amar M, Bacigalupo A et al (1993) Malignant tumors occurring after treatment of aplastic anemia. N Engl J Med 329:1152\u20131157. https:\/\/doi.org\/10.1056\/NEJM199310143291603","journal-title":"N Engl J Med"},{"key":"7062_CR8","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/S1246-7820(02)00277-X","volume":"10","author":"RY Dodd","year":"2003","unstructured":"Dodd RY (2003) Bacterial contamination and transfusion safety: experience in the United States. Transfus Clin Biol 10:6\u20139. https:\/\/doi.org\/10.1016\/S1246-7820(02)00277-X","journal-title":"Transfus Clin Biol"},{"key":"7062_CR9","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1097\/00062752-199704060-00020","volume":"4","author":"GS Sandler","year":"1997","unstructured":"Sandler GS (1997) Alloimmune refractoriness to platelet transfusions. Curr Opin Hematol 4:470\u2013473. https:\/\/doi.org\/10.1097\/00062752-199704060-00020","journal-title":"Curr Opin Hematol"},{"key":"7062_CR10","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1182\/hematology.2019000036","volume":"2019","author":"TD Coates","year":"2019","unstructured":"Coates TD (2019) Iron overload in transfusion-dependent patients. Hematology Am Soc Hematol Educ Program 2019:337\u2013344. https:\/\/doi.org\/10.1182\/hematology.2019000036","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"7062_CR11","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1182\/blood.V77.5.937.937","volume":"77","author":"S Kojima","year":"1991","unstructured":"Kojima S, Fukuda M, Miyajima Y, Matsuyama T, Horibe K (1991) Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor. Blood 77:937\u2013941. https:\/\/doi.org\/10.1182\/blood.V77.5.937.937","journal-title":"Blood"},{"key":"7062_CR12","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.3324\/haematol.2020.246512","volume":"105","author":"DJ Young","year":"2020","unstructured":"Young DJ, Dunbar CE (2020) Immunosuppression and growth factors for severe aplastic anemia: new data for old questions. Haematologica 105:1170\u20131171. https:\/\/doi.org\/10.3324\/haematol.2020.246512","journal-title":"Haematologica"},{"key":"7062_CR13","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/369568a0","volume":"369","author":"K Kaushansky","year":"1994","unstructured":"Kaushansky K, Lok S, Holly RD et al (1994) Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 369:568\u2013571. https:\/\/doi.org\/10.1038\/369568a0","journal-title":"Nature"},{"key":"7062_CR14","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1126\/science.8073287","volume":"265","author":"AL Gurney","year":"1994","unstructured":"Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW (1994) Thrombocytopenia in c-mpl-deficient mice. Science 265:1445\u20131447. https:\/\/doi.org\/10.1126\/science.8073287","journal-title":"Science"},{"key":"7062_CR15","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/S0140-6736(10)60959-2","volume":"377","author":"G Cheng","year":"2011","unstructured":"Cheng G, Saleh MN, Marcher C et al (2011) Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 377:393\u2013402. https:\/\/doi.org\/10.1016\/S0140-6736(10)60959-2","journal-title":"Lancet"},{"key":"7062_CR16","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1182\/blood-2008-04-150078","volume":"113","author":"JB Bussel","year":"2009","unstructured":"Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL (2009) Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 113:2161\u20132171. https:\/\/doi.org\/10.1182\/blood-2008-04-150078","journal-title":"Blood"},{"key":"7062_CR17","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/S0140-6736(08)60203-2","volume":"371","author":"DJ Kuter","year":"2008","unstructured":"Kuter DJ, Bussel JB, Lyons RM et al (2008) Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 371:395\u2013403. https:\/\/doi.org\/10.1016\/S0140-6736(08)60203-2","journal-title":"Lancet"},{"key":"7062_CR18","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1182\/blood.V87.6.2162.bloodjournal8762162","volume":"87","author":"WS Alexander","year":"1996","unstructured":"Alexander WS, Roberts AW, Nicola NA, Li R, Metcalf D (1996) Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood 87:2162\u20132170. https:\/\/doi.org\/10.1182\/blood.V87.6.2162.bloodjournal8762162","journal-title":"Blood"},{"key":"7062_CR19","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1182\/blood.V88.3.803.803","volume":"88","author":"K Carver-Moore","year":"1996","unstructured":"Carver-Moore K, Broxmeyer HE, Luoh SM et al (1996) Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-mpl-deficient mice. Blood 88:803\u2013808. https:\/\/doi.org\/10.1182\/blood.V88.3.803.803","journal-title":"Blood"},{"key":"7062_CR20","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1182\/blood.V92.1.4.413k38_4_10","volume":"92","author":"GP Solar","year":"1998","unstructured":"Solar GP, Kerr WG, Zeigler FC et al (1998) Role of c-mpl in early hematopoiesis. Blood 92:4\u201310. https:\/\/doi.org\/10.1182\/blood.V92.1.4.413k38_4_10","journal-title":"Blood"},{"key":"7062_CR21","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1182\/blood.V86.7.2494.2494","volume":"86","author":"M Kobayashi","year":"1995","unstructured":"Kobayashi M, Laver JH, Kato T, Miyazaki H, Ogawa M (1995) Recombinant human thrombopoietin (Mpl ligand) enhances proliferation of erythroid progenitors. Blood 86:2494\u20132499. https:\/\/doi.org\/10.1182\/blood.V86.7.2494.2494","journal-title":"Blood"},{"key":"7062_CR22","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1172\/JCI118210","volume":"96","author":"K Kaushansky","year":"1995","unstructured":"Kaushansky K, Broudy VC, Grossmann A et al (1995) Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy. J Clin Invest 96:1683\u20131687. https:\/\/doi.org\/10.1172\/JCI118210","journal-title":"J Clin Invest"},{"key":"7062_CR23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/nejmoa1200931","volume":"367","author":"MJ Olnes","year":"2012","unstructured":"Olnes MJ, Scheinberg P, Calvo KR et al (2012) Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 367:11\u201319. https:\/\/doi.org\/10.1056\/nejmoa1200931","journal-title":"N Engl J Med"},{"key":"7062_CR24","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1182\/blood-2013-10-534743","volume":"123","author":"R Desmond","year":"2014","unstructured":"Desmond R, Townsley DM, Dumitriu B et al (2014) Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 123:1818\u20131825. https:\/\/doi.org\/10.1182\/blood-2013-10-534743","journal-title":"Blood"},{"key":"7062_CR25","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1056\/NEJMoa1613878","volume":"376","author":"DM Townsley","year":"2017","unstructured":"Townsley DM, Scheinberg P, Winkler T et al (2017) Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 376:1540\u20131550. https:\/\/doi.org\/10.1056\/NEJMoa1613878","journal-title":"N Engl J Med"},{"key":"7062_CR26","doi-asserted-by":"publisher","first-page":"5732","DOI":"10.1182\/bloodadvances.2024014855","volume":"9","author":"JW Lee","year":"2025","unstructured":"Lee JW, Jang JH, Yamazaki H et al (2025) Addition of romiplostim to immunosuppressive therapy as first-line treatment for patients with aplastic anemia. Blood Adv 9:5732\u20135735. https:\/\/doi.org\/10.1182\/bloodadvances.2024014855","journal-title":"Blood Adv"},{"key":"7062_CR27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.cyto.2003.05.001","volume":"25","author":"VC Broudy","year":"2004","unstructured":"Broudy VC, Lin NL (2004) AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine 25:52\u201360. https:\/\/doi.org\/10.1016\/j.cyto.2003.05.001","journal-title":"Cytokine"},{"key":"7062_CR28","doi-asserted-by":"publisher","first-page":"e562","DOI":"10.1016\/S2352-3026(19)30153-X","volume":"6","author":"JW Lee","year":"2019","unstructured":"Lee JW, Lee SE, Jung CW et al (2019) Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. Lancet Haematol 6:e562\u2013e572. https:\/\/doi.org\/10.1016\/S2352-3026(19)30153-X","journal-title":"Lancet Haematol"},{"key":"7062_CR29","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/bjh.17190","volume":"192","author":"JH Jang","year":"2021","unstructured":"Jang JH, Tomiyama Y, Miyazaki K et al (2021) Efficacy and safety of romiplostim in refractory aplastic anaemia: a phase II\/III, multicentre, open-label study. Br J Haematol 192:190\u2013199. https:\/\/doi.org\/10.1111\/bjh.17190","journal-title":"Br J Haematol"},{"key":"7062_CR30","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41375-020-0950-6","volume":"35","author":"K Hosokawa","year":"2021","unstructured":"Hosokawa K, Yamazaki H, Tanabe M, Imi T, Sugimori N, Nakao S (2021) High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag. Leukemia 35:906\u2013909. https:\/\/doi.org\/10.1038\/s41375-020-0950-6","journal-title":"Leukemia"},{"key":"7062_CR31","unstructured":"Kyowa Kirin Company Ltd (2025) Romiplate\u00ae, package insert [in Japanese]. https:\/\/medical.kyowakirin.co.jp\/site\/drugpdf\/tenpupdf\/rpt.pdf. Accessed 9 February 2026"},{"key":"7062_CR32","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s12185-015-1787-z","volume":"101","author":"M Miano","year":"2015","unstructured":"Miano M, Dufour C (2015) The diagnosis and treatment of aplastic anemia: a review. Int J Hematol 101:527\u2013535. https:\/\/doi.org\/10.1007\/s12185-015-1787-z","journal-title":"Int J Hematol"},{"key":"7062_CR33","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2024.2335419","volume":"29","author":"H Guo","year":"2024","unstructured":"Guo H, Liu C, Kang L, Liu C, Liu Y (2024) Safety and efficacy of eltrombopag in patients with aplastic anemia: a systematic review and meta-analysis of randomized controlled trials. Hematology 29:2335419. https:\/\/doi.org\/10.1080\/16078454.2024.2335419","journal-title":"Hematology"},{"key":"7062_CR34","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1182\/blood.V86.11.4025.bloodjournal86114025","volume":"86","author":"XQ Yan","year":"1995","unstructured":"Yan XQ, Lacey D, Fletcher F et al (1995) Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice. Blood 86:4025\u20134033. https:\/\/doi.org\/10.1182\/blood.V86.11.4025.bloodjournal86114025","journal-title":"Blood"},{"key":"7062_CR35","doi-asserted-by":"publisher","first-page":"3748","DOI":"10.1182\/blood-2009-05-224766","volume":"114","author":"DJ Kuter","year":"2009","unstructured":"Kuter DJ, Mufti GJ, Bain BJ, Hasserjian RP, Davis W, Rutstein M (2009) Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 114:3748\u20133756. https:\/\/doi.org\/10.1182\/blood-2009-05-224766","journal-title":"Blood"},{"key":"7062_CR36","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.3324\/haematol.2018.212845","volume":"104","author":"W Ghanima","year":"2019","unstructured":"Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB (2019) Thrombopoietin receptor agonists: ten years later. Haematologica 104:1112\u20131123. https:\/\/doi.org\/10.3324\/haematol.2018.212845","journal-title":"Haematologica"},{"key":"7062_CR37","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1182\/blood.2019000940","volume":"136","author":"L Sun","year":"2020","unstructured":"Sun L, Babushok DV (2020) Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood 136:36\u201349. https:\/\/doi.org\/10.1182\/blood.2019000940","journal-title":"Blood"},{"key":"7062_CR38","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1182\/blood.2019000478","volume":"133","author":"T Winkler","year":"2019","unstructured":"Winkler T, Fan X, Cooper J et al (2019) Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 133:2575\u20132585. https:\/\/doi.org\/10.1182\/blood.2019000478","journal-title":"Blood"},{"key":"7062_CR39","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1007\/s12185-020-02971-1","volume":"112","author":"M Ise","year":"2020","unstructured":"Ise M, Iizuka H, Kamoda Y, Hirao M, Kida M, Usuki K (2020) Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Int J Hematol 112:787\u2013794. https:\/\/doi.org\/10.1007\/s12185-020-02971-1","journal-title":"Int J Hematol"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-07062-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07062-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07062-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:55:16Z","timestamp":1788317716000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-07062-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["7062"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-07062-5","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"25 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The protocol was reviewed and approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Following approval by the director of each medical institution, the study was conducted in compliance with the Declaration of Helsinki and the Japanese Ministerial Ordinance on Good Post-Marketing Study Practice (GPSP).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent from patients was not obtained because this requirement is waived under the GPSP ordinance. All medical institutions using romiplostim to treat patients with refractory AA were informed of the study protocol and provided written consent to publish anonymized results.","order":2,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Itagaki M received honoraria from Kyowa Kirin Co., Ltd., Alexion Pharma GK, and Janssen Pharmaceutical K.K., and consulting fees for the present manuscript from Kyowa Kirin Co., Ltd. Kuwazawa H, Sasaki S, Matsuura M, and Tanaka Y are employees of Kyowa Kirin Co., Ltd. Obara N received honoraria from Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Alexion Pharma GK and received commissioned research and joint research funding from Alexion Pharma GK, and consulting fees for the present manuscript from Kyowa Kirin Co., Ltd.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"349"}}