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FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan Children’s Cancer Group

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Abstract

Nelarabine is a key drug for T-cell acute lymphoblastic leukemia (T-ALL). Fludarabine and etoposide might have synergistic effect with nelarabine by inhibiting ribonucleotide reductase and by preparing cell cycle for G1/S phase, respectively. We had started phase 1/2 multicenter clinical trial of combination chemotherapy consisted of nelarabine, fludarabine, and etoposide (FLEND therapy) for children with relapsed/refractory T-ALL which has been conducted since October 2011. Although we could not complete this trial because of recruitment difficulties, we treated five children with first-relapsed T-ALL which were enrolled in the phase 1 dose escalation study of fludarabine and etoposide with nelarabine. No dose-limiting toxicity occurred, and frequent grade 3–4 toxicity was hematological toxicity and febrile neutropenia, as expected. There was no neurotoxicity. All 2 patients who received the target dose of FLEND, in which nelarabine (650 mg/m2), fludarabine (30 mg/m2), and etoposide (100 mg/m2) were administered for 5 consecutive days, were induced to complete remission. We concluded that FLEND might be safe and one of the promising combination chemotherapies to relapsed/refractory T-ALL.

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Acknowledgements

We are indebted to the staff of all participating institutions and thank all patients/parents/guardians for their willingness to participate in the ALL-RT11 trial. We also thank Koji Kato, Tadashi Iwasa, Takahiro Aoki, Keitaroh Fukushima, Kaori Fukushima, and Akiyama Kosuke for making Case Report Forms.

Funding

Funding was provided by Ministry of Health, Labour and Welfare (Grant no. H23-GanRinsho-Ippan-014) and Japan Agency for Medical Research and Development (Grant no. 16ck0106071h0003).

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Authors and Affiliations

  1. Department of Pediatric Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Tadashi Kumamoto & Chitose Ogawa

  2. Department of Hematology and Oncology, Children’s Cancer Center, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hiroaki Goto

  3. Department of Pediatrics, Aich Medical University Hospital, Nagoya, Japan

    Toshinori Hori

  4. Division of Cancer Immunodiagnostics, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Takao Deguchi

  5. Department of Clinical Pharmacology and Therapeutics, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Takuya Araki

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

    Akiko M. Saito & Keizo Horibe

  7. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Atsushi Manabe

  8. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Hidemi Toyoda

Authors
  1. Tadashi Kumamoto
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  2. Hiroaki Goto
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  3. Chitose Ogawa
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  4. Toshinori Hori
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  5. Takao Deguchi
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  6. Takuya Araki
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  7. Akiko M. Saito
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  8. Atsushi Manabe
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  9. Keizo Horibe
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  10. Hidemi Toyoda
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Corresponding author

Correspondence to Tadashi Kumamoto.

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Kumamoto, T., Goto, H., Ogawa, C. et al. FLEND (nelarabine, fludarabine, and etoposide) for relapsed T-cell acute lymphoblastic leukemia in children: a report from Japan Children’s Cancer Group. Int J Hematol 112, 720–724 (2020). https://doi.org/10.1007/s12185-020-02962-2

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  • DOI: https://doi.org/10.1007/s12185-020-02962-2

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