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Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16

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Abstract

The survival rate of children with acute lymphoblastic leukemia (ALL) has increased to approximately 90% after substantial progress in risk-oriented treatment strategies. Between 2005 and 2013, the Tokyo Children’s Cancer Study Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The principal aim of this study was to assemble background characteristics and treatment outcomes, and gather genetic information on leukemic cells under central diagnosis. This report outlines the background characteristics and treatment outcomes of 1033 children with ALL treated according to a TCCSG platform. The 5-year event-free and overall survival (OS) rates for all children were 78.1 ± 1.3 and 89.6 ± 1.0%, respectively. The OS rate was significantly higher in children with B-cell precursor (BCP)-ALL (91.9 ± 1.0%, n = 916) than in those with T-ALL (71.9 ± 4.3%, n = 117, p < 0.001). In univariate analysis for BCP-ALL, children aged 1–6 years (5y-OS: 94.2 ± 1.0%), with an initial white blood cell count of < 20,000/μL (94.0 ± 1.0%), high hyperdiploidy (95.4 ± 1.6%), ETV6-RUNX1 (97.4 ± 1.2%) or TCF3-PBX1 (96.9 ± 2.1%), and “Day8NoBlasts” (96.4 ± 1.1%) had the best outcomes. Genetic investigation revealed two novel fusion genes within this cohort: ETV6-ZNF385A and ZNF362-TCF4. Our study highlighted the clinical aspects of genomic features of ALL in Japanese children. We provide fundamental information for the further molecular investigation of this disease.

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Acknowledgements

The authors would like to thank the participating institutes and physicians in the TCCSG. They would also like to thank Ms. Kaori Itagaki for preparing and refining the protocol data. This work was supported, in part, by grants from the Children’s Cancer Association of Japan and the Grant of the National Center for Child Health and Development (26-20).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan

    Hiroyuki Takahashi & Akira Ohara

  2. Department of Pediatrics, Yokohama City University, Yokohama, Japan

    Ryosuke Kajiwara

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

    Motohiro Kato & Daisuke Tomizawa

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

    Daisuke Hasegawa & Atsushi Manabe

  5. Department of Pediatrics, Japanese Red Cross Narita Hospital, Narita, Japan

    Yasushi Noguchi

  6. Division of Pediatric Hematology and Oncology, Ibaraki Children’s Hospital, Mito, Japan

    Kazutoshi Koike

  7. Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan

    Daisuke Toyama

  8. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan

    Hiromasa Yabe

  9. Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan

    Michiko Kajiwara

  10. Department of Pediatrics, Juntendo University, Tokyo, Japan

    Junya Fujimura

  11. Department of Pediatrics, Gunma Children’s Medical Center, Shibukawa, Japan

    Manabu Sotomatsu

  12. Department of Pediatrics, Teikyo University Chiba Medical Center, Ichihara, Japan

    Setsuo Ota

  13. Department of Pediatrics, Nippon Medical School, Tokyo, Japan

    Miho Maeda

  14. Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  15. Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan

    Yoko Kato

  16. Department of Pediatrics, St. Marianna University, Kawasaki, Japan

    Tetsuya Mori

  17. Department of Pediatrics, University of Yamanashi, Chuo, Japan

    Takeshi Inukai

  18. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan

    Hiroyuki Shimada

  19. Department of Pediatrics, Dokkyo Medical University, Shimotsuga, Japan

    Keitaro Fukushima

  20. Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan

    Chitose Ogawa

  21. Department of Hematology-Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Atsushi Makimoto

  22. Department of Pediatrics, University of Tsukuba, Tsukuba, Japan

    Takashi Fukushima

  23. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan

    Kentaro Ohki & Nobutaka Kiyokawa

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

    Katsuyoshi Koh

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  1. Hiroyuki Takahashi
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Correspondence to Hiroyuki Takahashi.

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The authors declare that they have no conflicts of interest.

Additional information

Dr. Atsushi Makimoto was affilated to Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan (belonged till February 2013).

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Takahashi, H., Kajiwara, R., Kato, M. et al. Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16. Int J Hematol 108, 98–108 (2018). https://doi.org/10.1007/s12185-018-2440-4

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  • DOI: https://doi.org/10.1007/s12185-018-2440-4

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