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Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study

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Abstract

Chronic lymphocytic leukemia (CLL) is rare in Japan. We conducted the nationwide, prospective observational study CLLRSG-01 to clarify the current state of CLL in Japan and to make accurate international comparisons by preparing naturally air-dried smears like those used in other countries. Of the 201 untreated patients enrolled and evaluated, 119 were diagnosed with CLL and 82 with non-CLL mature B-cell neoplasms, based on the WHO classification. Of the 119 CLL patients, 90 were classified as typical and 29 as atypical according to FAB classification morphology, with the proportion of atypical CLL consistent with reports from other countries. Immunophenotypic analyses by flow cytometry showed that 55% of Japanese CLL patients had a Matutes score of 4 or higher, which is lower than the rate of about 90% in Europeans. Mutated IGHV was identified in 80% of Japanese CLL patients, which is a higher rate than in Western patients. The most frequent IGHV gene was VH3-30 (15%), followed by VH3-23 (12%) and VH4-34 (10%). VH1-69, the most common gene in Western countries, was identified in only one patient. These results indicate that the pattern of immunophenotypes and IGHV gene usage in Japanese CLL patients differs from that in Western patients.

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Acknowledgements

The authors would like to thank all of the patients who participated in this study.

Funding

This study was supported by JSPS KAKENHI Grant (Grant-in-Aid for Scientific Research (C)) Numbers 16K08963, 19K07863, 23K06848.

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Authors and Affiliations

  1. Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine, Niigata University, Niigata, Japan

    Jun Takizawa

  2. Shimane University Hospital, Cancer Center, Izumo, Japan

    Ritsuro Suzuki & Junji Suzumiya

  3. Department of Hematology and Oncology, Shimane University School of Medicine, Izumo, Japan

    Ritsuro Suzuki

  4. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Koji Izutsu

  5. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan

    Koji Izutsu

  6. Department of Hematology, Chugoku Central Hospital, Fukuyama, Japan

    Toru Kiguchi & Taro Masunari

  7. Division of Diabetes, Endocrinology and Hematology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan

    Toru Kiguchi

  8. Department of Hematology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Hideki Asaoku

  9. Department of Hematology, Oita Prefectural Hospital, Oita, Japan

    Yoshio Saburi

  10. Department of Hematology, Imamura General Hospital, Kagoshima, Japan

    Atae Utsunomiya

  11. Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    Kengo Takeuchi

  12. Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    Kengo Takeuchi

  13. Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Kengo Takeuchi

  14. Department of Pathology, Tokai University, Isehara, Japan

    Naoya Nakamura

  15. Department of Pathology, Kurume University, Kurume, Japan

    Koichi Ohshima

  16. Department of Internal Medicine 1, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria

    Michaela Gruber & Ulrich Jäger

  17. Pathophysiology, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan

    Sadao Aoki

  18. Department of Hematology, Koga Community Hospital, Shizuoka, Japan

    Junji Suzumiya

Authors
  1. Jun Takizawa
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  2. Ritsuro Suzuki
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  3. Koji Izutsu
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  8. Atae Utsunomiya
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  15. Junji Suzumiya
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Corresponding author

Correspondence to Jun Takizawa.

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Conflict of interest

Jun Takizawa: Honoraria from AstraZeneca, AbbVie, Janssen, Novartis, Chugai, Kyowa-Kirin, Ono, Eisai, Nippon Kayaku; research funding from AstraZeneca, AbbVie, Janssen, Novartis, Chugai, Yakult, Kyowa-Kirin, Ono, Eisai, Nippon Shinyaku, Asahi Kasei, Nippon Kayaku. Ritsuro Suzuki: Chugai, Kyowa-Kirin, Abbvie, Bristol-Meyer Squib, Eisai, MSD, Janssen, Takeda, Meiji-Seika, Ohtsuka, Novartis, AstraZeneca; research funding from Chugai, Kyowa-Kirin, Shionogi, Taiho, Ohtsuka. Koji Izutsu: Honoraria from Bristol Myers Squibb, AstraZeneca, Janssen, Eisai, Kyowa-Kirin, Takeda, Chugai, Novartis, MSD, Symbio, AbbVie, Ono, Pfizer, Eli lily, Daiichi Sankyo; consulting role for Bristol Myers Squibb, AstraZeneca, Zenyaku, MSD, Nippon Shinyaku, AbbVie, Ono, Genmab, Mitsubishi Tanabe Pharma, Nippon Kayaku; research funding from MSD, AstraZeneca, AbbVie, Eisai, Incyte, Bristol Myers Squibb, Novartis, Pfizer, Janssen, Yakult, Kyowa-Kirin, Ono, Daiichi Sankyo, Chugai, Beigene, LOXO Oncology, Otsuka, Regeneron. Toru Kiguchi: Honoraria from Bristol-Meyer Squib, Astellas, Novartis, Nippon Shinyaku, Symbio, AbbVie; consulting role for Astellas. Atae Utsunomiya: Honoraria from Meiji-Seika, Kyowa-Kirin, Bristol-Meyer Squib; consulting role for JIMRO, HUYA Japan, Otsuka Medical Devices. Kengo Takeuchi: Honoraria from Eli Lilly, Chugai, Kyowa-Kirin, Janssen; research funding from Fujirebio, SONY, Daiichi Sankyo; consulting role for Nichirei Bioscience, Nippon Shinyaku, Meiji-Seika; Royalties or licenses from Sysmex, AMOY, Nichirei Bioscience. Ulrich Jäger: Honoraria from Roche, Abbvie, Janssen, Beigene, Novartis, and BMS; consulting role for Roche. Sadao Aoki: Honoraria from AstraZeneca, Janssen. Junji Suzumiya: Honoraria from Abbvie, AstraZeneca, Bristol Myers Squibb, Chugai, Dainihon-Sumitomo, Eli Lill, Janssen, Kyowa-Kirin, Novartis, Ootsuka, SymBio, Takeda, Zenyaku, Tanabe-Mitsubishi; consulting role for Abbvie, Chugai, Janssen, Kyowa-Kirin, Nippon Shinyaku, Ootsuka, SymBio, Zenyaku. The other authors have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of Shimane University (#2805) and all participating institutions.

Informed consent

Written informed consent was obtained from all subjects enrolled in the study.

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Takizawa, J., Suzuki, R., Izutsu, K. et al. Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study. Int J Hematol (2024). https://doi.org/10.1007/s12185-024-03741-z

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  • DOI: https://doi.org/10.1007/s12185-024-03741-z

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