The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who und
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ORIGINAL ARTICLE
The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation Takayoshi Tachibana 1 & Yuho Najima 2 & Yu Akahoshi 3 & Shigeki Hirabayashi 4 & Kaito Harada 5 & Noriko Doki 2 & Naoyuki Uchida 6 & Takahiro Fukuda 7 & Masashi Sawa 8 & Masao Ogata 9 & Satoru Takada 10 & Masatsugu Tanaka 1 & Yoshiko Matsuhashi 11 & Junji Tanaka 12 & Makoto Onizuka 5 & Tatsuo Ichinohe 13 & Yoshiko Atsuta 14 & Shinichi Kako 3 & On Behalf of the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation Received: 3 June 2020 / Accepted: 1 August 2020 / Published online: 15 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCRABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16–70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1–125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p < 0.001; relapse rate [RR]: 48% vs 18%, p < 0.001), particularly with the presence of the T315I mutation (OS: 29% vs 68%, p < 0.001; RR: 54% vs 18%, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological (p < 0.001) or molecular complete remission (p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95% confidence interval [CI]: 1.5–3.3, p < 0.001; RR: HR = 2.51, 95% CI: 1.5–4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL. Keywords BCR-ABL1 . Mutation . T315I . Ph + ALL . Allogeneic hematopoietic cell transplantation . Prognosis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04212-1) contains supplementary material, which is available to authorized users. * Takayoshi Tachibana [email protected] 1
Department of Hematology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan
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Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
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Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
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Department of Hematology, Oita University Hospital, Oita, Japan Leukemia Research Center, Saiseikai Mabashi Hospital, Gunma, Japan
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Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
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Division of Hematology, Jichi Medical University Saitama Medical Center,
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