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Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome-positive acute lymphoblastic leukemia.

  • Akahoshi, Yu1
  • Nishiwaki, Satoshi2
  • Mizuta, Shuichi3
  • Ohashi, Kazuteru4
  • Uchida, Naoyuki5
  • Tanaka, Masatsugu6
  • Fukuda, Takahiro7
  • Ozawa, Yukiyasu8
  • Takahashi, Satoshi9
  • Onizuka, Makoto10
  • Shiratori, Souichi11
  • Nakamae, Hirohisa12
  • Kanda, Yoshinobu1, 13
  • Ichinohe, Tatsuo14
  • Atsuta, Yoshiko15
  • Kako, Shinichi1
  • 1 Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan. , (Japan)
  • 2 Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan. , (Japan)
  • 3 Department of Hematology & Immunology, Kanazawa Medical University, Ishikawa, Japan. , (Japan)
  • 4 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan. , (Japan)
  • 5 Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan. , (Japan)
  • 6 Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan. , (Japan)
  • 7 Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. , (Japan)
  • 8 Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. , (Japan)
  • 9 Division of Molecular Therapy, The Advanced Clinical Research Centre, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. , (Japan)
  • 10 Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan. , (Japan)
  • 11 Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan. , (Japan)
  • 12 Department of Hematology, Osaka City University Graduate School of Medicine, Osaka, Japan. , (Japan)
  • 13 Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan. , (Japan)
  • 14 Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. , (Japan)
  • 15 Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan. , (Japan)
Published Article
Cancer science
Publication Date
Oct 01, 2019
DOI: 10.1111/cas.14167
PMID: 31402561


Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative-minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative-MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive-MRD with complete remission [CR] and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative-MRD or positive-MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new-generation TKI for high-risk patients are warranted to improve the outcomes after allogeneic HSCT. © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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