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JACLS ALL-02 SR protocol reduced-intensity chemotherapy produces excellent outcomes in patients with low-risk childhood acute lymphoblastic leukemia

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Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. As overall cure rates of childhood ALL have improved, reduction of overall treatment intensity while still ensuring excellent outcomes is imperative for low-risk patients. We report the outcomes of patients treated following the standard-risk protocol from the prospective Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study, which was conducted between 2002 and 2008 for patients with newly diagnosed ALL aged 1–18 years. Of 1138 patients with B-cell precursor ALL, 388 (34.1%) were allocated to this protocol. Excellent outcomes were achieved despite the overall treatment intensity being lower than that of most contemporary protocols: 4 years event-free survival (EFS) was 92.3% and 4 years overall survival 98.2%. Patients with high hyperdiploidy (HHD) involving triple trisomy (trisomy of chromosomes 4, 10, and 17) or ETV6-RUNX1 had even better outcomes (4 years EFS 97.6% and 100%, respectively). Unique characteristics of this protocol include a selection of low-risk patients with a low initial WBC count and good early treatment response and reduction of cumulative doses of chemotherapeutic agents while maintaining dose density. In Japan, we are currently investigating the feasibility of this protocol while incorporating minimal residual disease into the patient stratification strategy.

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Acknowledgements

The authors thank the patients who participated in this study. In addition, the authors thank all physicians, nurses, and support personnel for their dedicated care of patients in this study.

Funding

Ministry of Health, Labour and Welfare, H14-Koka (Gan)- 031, Keizo Horibe, H15-Koka (Gan)-024, Keizo Horibe, H16-GanRinsho-004, Keizo Horibe, H17-GanRinsho-004., Keizo Horibe.

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Author notes

  1. Yoshihiro Takahashi and Hisashi Ishida have contributed equally.

Authors and Affiliations

  1. Department of Pediatrics, Aomori Prefectural Central Hospital, Aomori, Japan

    Yoshihiro Takahashi

  2. Department of Pediatrics, Okayama University Hospital, Okayama, Japan

    Hisashi Ishida, Kosuke Tamefusa & Megumi Oda

  3. Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465, Kajiichou, Hirokouji Kawaramachidori, Kamigyo-ku, Kyoto, 602-8566, Japan

    Toshihiko Imamura

  4. Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University Faculty of Medicine, Oita, Japan

    Souichi Suenobu

  5. Department of Pediatric Hematology and Oncology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan

    Ikuya Usami

  6. Yumura Clinic, Osaka, Japan

    Keiko Yumura-Yagi

  7. Department of Hematology/Oncology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Daiichiro Hasegawa & Yoshiyuki Kosaka

  8. Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan

    Shinichiro Nishimura

  9. Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan

    Nobuhiro Suzuki

  10. Department of Pediatrics, Osaka University, Suita, Japan

    Yoshiko Hashii

  11. Department of Pediatrics, Mie University, Tsu, Japan

    Takao Deguchi & Hiroki Hori

  12. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Akiko Moriya-Saito & Keizo Horibe

  13. Department of Hematology Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koji Kato

  14. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan

    Ryoji Kobayashi

  15. Department of Pediatrics, Kansai Medical University, Hirakata, Japan

    Hirohide Kawasaki

  16. Department of Hematology/Oncology, Miyagi Children’s Hospital, Sendai, Japan

    Atsushi Sato

  17. Saiseikai Nishiotaru Hospital, Otaru, Japan

    Toru Kudo

  18. Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Tatsutoshi Nakahata

  19. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan

    Junichi Hara

Authors
  1. Yoshihiro Takahashi
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  2. Hisashi Ishida
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  3. Toshihiko Imamura
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  4. Kosuke Tamefusa
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  7. Keiko Yumura-Yagi
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  8. Daiichiro Hasegawa
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  12. Takao Deguchi
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  14. Yoshiyuki Kosaka
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  15. Koji Kato
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  17. Hirohide Kawasaki
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  18. Hiroki Hori
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  19. Atsushi Sato
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  20. Toru Kudo
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  21. Tatsutoshi Nakahata
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  22. Megumi Oda
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  23. Junichi Hara
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  24. Keizo Horibe
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Corresponding author

Correspondence to Toshihiko Imamura.

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Takahashi, Y., Ishida, H., Imamura, T. et al. JACLS ALL-02 SR protocol reduced-intensity chemotherapy produces excellent outcomes in patients with low-risk childhood acute lymphoblastic leukemia. Int J Hematol 115, 890–897 (2022). https://doi.org/10.1007/s12185-022-03315-x

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  • DOI: https://doi.org/10.1007/s12185-022-03315-x

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