{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:45:38Z","timestamp":1788468338210,"version":"build-2803163510"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Pfizer Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aplastic anemia results from lymphocyte-mediated destruction of hematopoietic stem cells. Immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is the standard front-line treatment for patients with severe aplastic anemia who are not suitable candidates for stem cell transplants. PF-06462700 is a potent equine ATG that targets T-lymphocytes and has been approved as a treatment for aplastic anemia outside of Japan for over 30\u00a0years. Due to the high medical need for PF-06462700, the Ministry of Health, Labor and Welfare requested its development for Japanese patients with aplastic anemia. In this case series, the efficacy and safety of PF-06462700, administered intravenously at 40\u00a0mg\/kg\/day for 4\u00a0days, were assessed over a 24-week period. This was as an open-label, single-arm, multicenter clinical study designed to enroll a minimum of three Japanese participants with aplastic anemia. Two participants met the primary outcome of hematologic response at week 12 and improvements in disease severity were observed. No deaths or serious adverse events were reported. The efficacy results from this case series suggest that administration of PF-06462700 is generally well-tolerated and produces a hematologic response in Japanese patients with aplastic anemia, which should be further evaluated in real-world studies.<\/jats:p><jats:p>ClinicalTrials.gov identifier: NCT04350606.<\/jats:p>","DOI":"10.1007\/s12185-022-03496-5","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T16:03:27Z","timestamp":1669651407000},"page":"37-43","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of equine anti-thymocyte immunoglobulin (eATG) in three Japanese patients with moderate to very severe aplastic anemia: a case series"],"prefix":"10.1007","volume":"117","clinical-trial-number":[{"clinical-trial-number":"nct04350606","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-9307","authenticated-orcid":false,"given":"Yoshinobu","family":"Kanda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Yoshimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"3496_CR1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s11864-017-0511-z","volume":"18","author":"SA Peslak","year":"2017","unstructured":"Peslak SA, Olson T, Babushok DV. Diagnosis and treatment of aplastic anemia. Curr Treat Options Oncol. 2017;18:70.","journal-title":"Curr Treat Options Oncol"},{"key":"3496_CR2","doi-asserted-by":"publisher","first-page":"i178","DOI":"10.1093\/ije\/dyv096.259","volume":"44","author":"A Ohta","year":"2015","unstructured":"Ohta A, Nagai M, Nishina M, Shimada N, Nakao S, Kurokawa M. Incidence of aplastic anemia in Japan: analysis of data from a nationwide registration system. Int J Epidemiol. 2015;44:i178-i.","journal-title":"Int J Epidemiol"},{"key":"3496_CR3","doi-asserted-by":"publisher","first-page":"518","DOI":"10.3324\/haematol.12020","volume":"93","author":"E Montane","year":"2008","unstructured":"Montane E, Ibanez L, Vidal X, Ballarin E, Puig R, Garcia N, et al. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008;93:518\u201323.","journal-title":"Haematologica"},{"key":"3496_CR4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00277-003-0781-3","volume":"83","author":"LY Bai","year":"2004","unstructured":"Bai LY, Chiou TJ, Liu JH, Yen CC, Wang WS, Yan MH, et al. Hematopoietic stem cell transplantation for severe aplastic anemia\u2013experience of an institute in Taiwan. Ann Hematol. 2004;83:38\u201343.","journal-title":"Ann Hematol"},{"key":"3496_CR5","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1056\/NEJM199105093241901","volume":"324","author":"N Frickhofen","year":"1991","unstructured":"Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A, Vogt HG, Herrmann F, et al. Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. N Engl J Med. 1991;324:1297\u2013304.","journal-title":"N Engl J Med"},{"key":"3496_CR6","unstructured":"Pfizer Inc. Highlights of prescribing information: ATGAM. 2021. http:\/\/labeling.pfizer.com\/ShowLabeling.aspx?id=525. Accessed 5 Oct 2021."},{"key":"3496_CR7","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1056\/NEJMoa1103975","volume":"365","author":"P Scheinberg","year":"2011","unstructured":"Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365:430\u20138.","journal-title":"N Engl J Med"},{"key":"3496_CR8","first-page":"353","volume":"107","author":"KF Mangan","year":"1986","unstructured":"Mangan KF, D\u2019Alessandro L, Mullaney MT. Action of antithymocyte globulin on normal human erythroid progenitor cell proliferation in vitro: erythropoietic growth-enhancing factors are released from marrow accessory cells. J Lab Clin Med. 1986;107:353\u201364.","journal-title":"J Lab Clin Med"},{"key":"3496_CR9","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1182\/blood.V78.1.163.163","volume":"78","author":"SD Nimer","year":"1991","unstructured":"Nimer SD, Golde DW, Kwan K, Lee K, Clark S, Champlin R. In vitro production of granulocyte-macrophage colony-stimulating factor in aplastic anemia: possible mechanisms of action of antithymocyte globulin. Blood. 1991;78:163\u20138.","journal-title":"Blood"},{"key":"3496_CR10","first-page":"1082","volume":"10","author":"K Kitamura","year":"1996","unstructured":"Kitamura K. Effect of anti-thymocyte globulin, U-ATG on aplastic anemia - a prospective multicenter randomized trial. Biotherapy (Tokyo). 1996;10:1082\u201395.","journal-title":"Biotherapy (Tokyo)"},{"key":"3496_CR11","unstructured":"Study Group on Idiopathic Hematopoietic Disorders Research Program on Rare and Intractable Diseases. Aplastic anemia reference guide 1-year revision. 2019. http:\/\/zoketsushogaihan.umin.jp\/file\/2020\/02.pdf. Accessed 11 Feb 2022."},{"key":"3496_CR12","doi-asserted-by":"publisher","first-page":"348","DOI":"10.3324\/haematol.13829","volume":"94","author":"P Scheinberg","year":"2009","unstructured":"Scheinberg P, Wu CO, Nunez O, Scheinberg P, Boss C, Sloand EM, et al. Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica. 2009;94:348\u201354.","journal-title":"Haematologica"},{"key":"3496_CR13","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1007\/s12185-016-2046-7","volume":"104","author":"T Suzuki","year":"2016","unstructured":"Suzuki T, Kobayashi H, Kawasaki Y, Okazuka K, Hatano K, Fujiwara S, et al. Efficacy of combination therapy with anti-thymocyte globulin and cyclosporine A as a first-line treatment in adult patients with aplastic anemia: a comparison of rabbit and horse formulations. Int J Hematol. 2016;104:446\u201353.","journal-title":"Int J Hematol"},{"key":"3496_CR14","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, Nagafuji K, Usuki K, Uoshima N, et al. Efficacy and safety of romiplostim in refractory aplastic anaemia: a phase II\/III, multicentre, open-label study. Br J Haematol. 2021;192:190\u20139.","journal-title":"Br J Haematol"},{"issue":"Suppl 1","key":"3496_CR15","first-page":"12","volume":"55","author":"RP de Latour","year":"2020","unstructured":"de Latour RP, Marsh J, Iacobelli S, Terwel S, Hill A, Halkes CJM, et al. The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Award Winners (O001) results of the Ebmt Saawp phase III prospective randomized multicenter race study of horse Atg and ciclosporin with or without eltrombopag in Naive Saa patients. Bone Marrow Transplant. 2020;55(Suppl 1):12\u201321.","journal-title":"Bone Marrow Transplant"}],"updated-by":[{"DOI":"10.1007\/s12185-023-03543-9","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000}}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-022-03496-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-022-03496-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-022-03496-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T07:16:11Z","timestamp":1674717371000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-022-03496-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["3496"],"URL":"https:\/\/doi.org\/10.1007\/s12185-022-03496-5","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s12185-023-03543-9","asserted-by":"object"}]},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"assertion":[{"value":"27 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2023","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s12185-023-03543-9","URL":"https:\/\/doi.org\/10.1007\/s12185-023-03543-9","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"YK, TM, and AN have no conflicts to declare. KDW is an employee and shareholder of Pfizer Inc. KN is an employee and shareholder of Pfizer R&D Japan. HY is an employee of Pfizer R&D Japan.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}