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Discontinuation of l-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia

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Abstract

ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reducing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol. The JACLS ALL-02 protocol does not employ minimal residual disease detected by polymerase chain reaction (PCR-MRD)-based risk stratification; however, 4-year event-free survival (EFS) and overall survival (OS) were 94.4 ± 1.6 and 97.5 ± 1.1%, respectively. In particular, 92 of 205 (44.9%) patients were successfully treated with a less intensive regimen involving only two cycles of high dose methotrexate and one course of re-induction therapy comprising vincristine, l-asparaginase (L-asp), pirarubicin, and prednisolone. Multivariate analysis revealed that discontinuation of L-asp and poor response to prednisolone was, respectively, associated with poor EFS (HR 6.3; 95% CI 1.3–27.0) and OS (HR 17.5; 95% CI 2.3–130), suggesting that the majority of ETV6-RUNX1-positive B-ALL cases may be cured by a less-intensive chemotherapy regimen if the risk stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.

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Acknowledgements

The authors thank all patients (and their guardians) who participated in this study. The authors also thank the staff at the OSCR data center for data management and all physicians who registered the patients in the JACLS ALL-02 clinical trial.

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Authors and Affiliations

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

    Ikuya Usami

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

    Ikuya Usami, Toshihiko Imamura, Akiko Moriya-Saito & Keizo Horibe

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

    Toshihiko Imamura

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

    Yoshihiro Takahashi

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

    So-ichi Suenobu

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

    Daiichiro Hasegawa

  7. Department of Pediatrics, Osaka University, Osaka, Japan

    Yoshiko Hashii

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

    Takao Deguchi & Hiroki Hori

  9. Department of Pediatrics, Sapporo Medical University of Medicine, Hokkaido, Japan

    Tsukasa Hori

  10. Department of Pediatrics, Okayama University, Okayama, Japan

    Akira Shimada

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

    Koji Kato

  12. Department of Pediatrics, Hirosaki University, Hirosaki, Japan

    Eturou Ito

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

    Hirohide Kawasaki

  14. Yumura Clinic, Osaka, Japan

    Keiko Yumura-Yagi

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

    Junichi Hara

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

    Atsushi Sato

Authors
  1. Ikuya Usami
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  2. Toshihiko Imamura
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  3. Yoshihiro Takahashi
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  4. So-ichi Suenobu
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  5. Daiichiro Hasegawa
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  6. Yoshiko Hashii
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  7. Takao Deguchi
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  8. Tsukasa Hori
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  9. Akira Shimada
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  10. Koji Kato
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  11. Eturou Ito
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  12. Akiko Moriya-Saito
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  13. Hirohide Kawasaki
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  14. Hiroki Hori
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  15. Keiko Yumura-Yagi
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  16. Junichi Hara
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  17. Atsushi Sato
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  18. Keizo Horibe
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Japan Association of Childhood Leukemia Study Group (JACLS)

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Correspondence to Toshihiko Imamura.

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Usami, I., Imamura, T., Takahashi, Y. et al. Discontinuation of l-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia. Int J Hematol 109, 477–482 (2019). https://doi.org/10.1007/s12185-019-02599-w

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  • DOI: https://doi.org/10.1007/s12185-019-02599-w

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