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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

  • Ikuya Usami
  • Toshihiko ImamuraEmail author
  • Yoshihiro Takahashi
  • So-ichi Suenobu
  • Daiichiro Hasegawa
  • Yoshiko Hashii
  • Takao Deguchi
  • Tsukasa Hori
  • Akira Shimada
  • Koji Kato
  • Eturou Ito
  • Akiko Moriya-Saito
  • Hirohide Kawasaki
  • Hiroki Hori
  • Keiko Yumura-Yagi
  • Junichi Hara
  • Atsushi Sato
  • Keizo Horibe
  • Japan Association of Childhood Leukemia Study Group (JACLS)
Original Article
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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.

Keywords

Poor prednisolone response l-asparaginase ETV6-RUNX1 Pediatric acute lymphoblastic leukemia 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Ikuya Usami
    • 1
    • 2
  • Toshihiko Imamura
    • 2
    • 3
    Email author
  • Yoshihiro Takahashi
    • 4
  • So-ichi Suenobu
    • 5
  • Daiichiro Hasegawa
    • 6
  • Yoshiko Hashii
    • 7
  • Takao Deguchi
    • 8
  • Tsukasa Hori
    • 9
  • Akira Shimada
    • 10
  • Koji Kato
    • 11
  • Eturou Ito
    • 12
  • Akiko Moriya-Saito
    • 2
  • Hirohide Kawasaki
    • 13
  • Hiroki Hori
    • 8
  • Keiko Yumura-Yagi
    • 14
  • Junichi Hara
    • 15
  • Atsushi Sato
    • 16
  • Keizo Horibe
    • 2
  • Japan Association of Childhood Leukemia Study Group (JACLS)
  1. 1.Department of Pediatric Hematology and OncologyHyogo Prefectural Amagasaki General Medical CenterHyogoJapan
  2. 2.Clinical Research CenterNational Hospital Organization Nagoya Medical CenterNagoyaJapan
  3. 3.Department of Pediatrics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  4. 4.Department of PediatricsAomori Prefectural Central HospitalAomoriJapan
  5. 5.Division of General Pediatrics and Emergency Medicine, Department of PediatricsOita UniversityOitaJapan
  6. 6.Department of Hematology/OncologyHyogo Prefectural Children’s HospitalKobeJapan
  7. 7.Department of PediatricsOsaka UniversityOsakaJapan
  8. 8.Department of PediatricsMie UniversityTsuJapan
  9. 9.Department of PediatricsSapporo Medical University of MedicineHokkaidoJapan
  10. 10.Department of PediatricsOkayama UniversityOkayamaJapan
  11. 11.Department of Hematology Oncology, Children’s Medical CenterJapanese Red Cross Nagoya First HospitalNagoyaJapan
  12. 12.Department of PediatricsHirosaki UniversityHirosakiJapan
  13. 13.Department of PediatricsKansai Medical UniversityHirakataJapan
  14. 14.Yumura ClinicOsakaJapan
  15. 15.Department of Pediatric Hematology/OncologyOsaka City General HospitalOsakaJapan
  16. 16.Department of Hematology/OncologyMiyagi Children’s HospitalSendaiJapan

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