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Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy

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Abstract

The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16–24 years and 25–65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG). In the HSCT-MRD group, patients younger than 25 years had lower overall survival (OS) than the 202U group, presumably due to the higher non-relapse mortality (NRM) in the HSCT-MRD group. Patients 25 years and older had similar OS to the 202O group. The lower relapse rate was counterbalanced by higher NRM in the HSCT-MRD group. In the HSCT-MUD group, patients in both age groups had similar OS to their corresponding groups in the JALSG studies. In conclusion, high-intensity chemotherapy may change the role of HSCT for Ph-negative ALL.

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Acknowledgements

The authors thank all the physicians and data managers of the JSTCT centers and the JALSG centers for providing excellent patient care and reporting clinical data to TRUMP and the JALSG studies. We also thank the staff of the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) for their assistance. This work was supported in part by a grant for Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP19ck0106331 and the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from AMED under Grant Number 19ek0510023h0002.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan

    Shinichi Kako

  2. Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Fumihiko Hayakawa

  3. Department of Hematology, Otaru General Hospital, Otaru, Japan

    Kiyotoshi Imai

  4. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Junji Tanaka

  5. Department of Immunology and Hematology, Kanazawa Medical University, Ishikawa, Japan

    Shuichi Mizuta

  6. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Satoshi Nishiwaki

  7. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Heiwa Kanamori

  8. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Junichi Mukae

  9. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  10. Department of Hematology, Kyoto University Hospital, Kyoto, Japan

    Tadakazu Kondo

  11. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  12. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

  13. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Shuichi Ota

  14. Third Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan

    Yoshinori Tanaka

  15. Department of Hematology, Hyogo Cancer Center, Akashi, Japan

    Tohru Murayama

  16. Division of Hematology and Oncology, Toyohashi Municipal Hospital, Aichi, Japan

    Shingo Kurahashi

  17. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan

    Toru Sakura

  18. Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Noriko Usui

  19. Kanazawa University, Kanazawa, Japan

    Shigeki Ohtake

  20. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hitoshi Kiyoi

  21. Department of Hematology/Rheumatology, Faculty of Medicine, Kindai University, Osakasayama, Japan

    Itaru Matsumura

  22. Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

    Yasushi Miyazaki

  23. Department of Healthcare Administration, Nagoya University, Nagoya, Japan

    Yoshiko Atsuta

  24. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

Authors
  1. Shinichi Kako
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  2. Fumihiko Hayakawa
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  8. Junichi Mukae
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Corresponding author

Correspondence to Shinichi Kako.

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Conflict of interest

Ota S has received honoraria from Novartis Pharma K.K. Usui N has received consulting fees from Cmic Co., Ltd., AbbVie GK, Nippon Shinyaku Co., Ltd., and Daiichi Sankyo Co., Ltd. and honoraria from Celgene Co., Ltd., SymBio Pharmaceuticals, Pfizer Japan Inc., Bristol-Myers Squibb, MundiPharma K.K., IQVIA Services Japan K.K., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Zenyaku Co., Ltd., and Taiho Pharmaceutical Co., Ltd. Kiyoi H has received research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Zenyaku Kogyo Co., Ltd., FUJIFILM Corporation, Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Eisai Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., Sanofi K.K., Perseus Proteomics Inc. and Celgene Corporation., consulting fees from Astellas Pharma Inc., Amgen Astellas BioPharma K.K., and Daiichi Sankyo Co., Ltd., and honoraria from Bristol-Myers Squibb, Astellas Pharma Inc., and Novartis Pharma K.K. Matsumura I has received research funding from Chugai Pharmaceutical Co., Ltd., Novartis Pharma KK, AbbVie GK., Takeda Pharmaceutical Company Limited., Pfizer Japan Inc., Eisai Co., Ltd., and MSD K.K. and honoraria from Novartis Pharma KK, Bristol-Myers Squibb Company, Pfizer Japan Inc., DAIICHI SANKYO COMPANY, LIMITED., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., and Amgen Astellas BioPharma K.K. Matsumura I also belonged to a laboratory supported, in part, by ONO PHARMACEUTICAL CO., LTD., Takeda Pharmaceutical Company Limited., Chugai Pharmaceutical Co., Ltd., NIPPON SHINYAKU CO.,LTD., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., AbbVie GK., ASAHI KASEI PHARMA CORPORATION, Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., TAIHO PHARMACEUTICAL CO., LTD., Sanofi K.K., Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma KK, and Astellas Pharma Inc.

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Kako, S., Hayakawa, F., Imai, K. et al. Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy. Int J Hematol 114, 608–619 (2021). https://doi.org/10.1007/s12185-021-03198-4

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