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Outcomes following induction failure in Japanese children with acute lymphoblastic leukemia

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Abstract

The characteristics and prognosis of Japanese children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission after remission induction chemotherapy (i.e., experience induction failure) are poorly understood. Therefore, we retrospectively analyzed data of patients enrolled in Japanese clinical trials for newly diagnosed ALL between 1996 and 2009. Among 4956 participants, 89 (1.8%) experienced induction failure. With a 6.0-year median follow-up, the 5-year overall survival rate of the entire cohort was 43.0% ± 5.5%. Survival rates did not differ between patients with B-cell precursor ALL (BCP-ALL) and T-cell ALL (T-ALL). In multivariate analysis, day 15 M3 marrow (bone marrow blast count ≥ 25%) was significantly correlated with poorer survival in the whole or BCP-ALL cohorts. In T-ALL, age < 6 years was significantly associated with poor survival. However, due to the small sample size, this correlation must be further investigated. Most T-ALL and BCR-ABL-positive BCP-ALL patients underwent allogeneic stem cell transplantation (allo-SCT). Survival rates did not differ between BCR-ABL-negative BCP-ALL patients who did and did not undergo allo-SCT, possibly due to the inclusion of lower-risk patients in the latter group. In conclusion, the induction failure rate and survival after diagnosis of induction failure in our study were comparable to previously reported figures.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. The request must be reviewed and approved by the four participating groups (CCLSG, KYCCSG, JACLS, TCCSG).

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Acknowledgements

We would like to thank all patients and their families. We acknowledge the work of the past and present members of the Childhood Cancer and Leukemia Study Group, Kyushu–Yamaguchi Childhood Cancer Study Group, Japan Association of Childhood Leukemia Study, Tokyo Children’s Cancer Study Group, Japan Pediatric Leukemia/Lymphoma Study Group, and Japan Children’s Cancer Group. We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuou-Ku, Niigata City, Niigata, 951-8510, Japan

    Chihaya Imai

  2. Department of Hematology and Oncology, Miyagi Children’s Hospital, Miyagi, Japan

    Atsushi Sato

  3. Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Mitsuteru Hiwatari

  4. Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan

    Mitsuteru Hiwatari

  5. Department of Pediatrics, Aichi Medical University, Aichi, Japan

    Yasuto Shimomura & Toshinori Hori

  6. Department of Pediatrics, Oita University, Oita, Japan

    Souichi Suenobu

  7. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Toshihiko Imamura

  8. Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan

    Junichi Hara

  9. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Daisuke Hasegawa

  10. Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan

    Hiroyuki Takahashi

  11. Department of Pediatrics, Tohoku University Graduate School of Medicine, Miyagi, Japan

    Kunihiko Moriya & Saori Katayama

  12. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Daisuke Tomizawa

  13. Department of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Hiroshi Moritake

  14. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan

    Takashi Taga

  15. Clinical Research Center, Nagoya Medical Center, Nagoya, Japan

    Keizo Horibe

  16. Department of Hematology/Oncology, Saitama Children’s Medical Center, Saitama, Japan

    Katsuyoshi Koh

  17. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

    Atsushi Manabe

  18. Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Yasuhiro Okamoto

Authors
  1. Chihaya Imai
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  2. Atsushi Sato
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  3. Mitsuteru Hiwatari
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  4. Yasuto Shimomura
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  7. Toshihiko Imamura
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  8. Junichi Hara
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  15. Takashi Taga
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  16. Keizo Horibe
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  17. Katsuyoshi Koh
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  18. Atsushi Manabe
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  19. Yasuhiro Okamoto
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Contributions

CI, AS, MH, YO, and AM designed the study; TH, YS, SS, TI, JH, DH, HT, KM, SK, DT, HM, TT, KH, and KK provided clinical data from each steering committee of the trials; CI, AS, MH, and YO contributed to the collection and management of individual patient data; CI performed statistical analyses; CI, AS, MH, and YO drafted the manuscript; and all authors have read and approved the final manuscript.

Corresponding author

Correspondence to Chihaya Imai.

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Conflict of interest

CI reports patent royalties from Juno Therapeutics, patent royalties, research funds, and advisory fees from CURED Inc. The other authors have no conflicts of interest to declare.

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Supplementary Information

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12185_2023_3600_MOESM1_ESM.pdf

Supplementary file1 Figure S1. The impact of the use of allogeneic stem cell transplantation on overall survival in non-BCR-ABL BCP-ALL. Kaplan–Meier analysis of OS in non-BCR-ABL BCP-ALL is shown. Black and red lines indicate patients treated with or without SCT, respectively. (PDF 52 KB)

Supplementary file2 (DOCX 24 KB)

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Imai, C., Sato, A., Hiwatari, M. et al. Outcomes following induction failure in Japanese children with acute lymphoblastic leukemia. Int J Hematol 118, 99–106 (2023). https://doi.org/10.1007/s12185-023-03600-3

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  • DOI: https://doi.org/10.1007/s12185-023-03600-3

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