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Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study

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Abstract

The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO− patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5–56.9] for RO+ and 69.7 % (58.4–81.1) for RO−, which was significantly superior to that in JLSG-96 [26.8 % (13.3–40.4) and 38.9 % (16.4–61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.

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Acknowledgments

The authors thank the many physicians who participated in the JLSG-02 study. We also thank Ms Yasuko Hashimoto for secretarial assistance. This work was supported by a Grant for Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare, Japan (Grant Reference Number: H24-General-076).

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Authors and Affiliations

  1. Department of Pediatrics, Jichi Medical University of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Akira Morimoto

  2. Pediatric Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Yoko Shioda

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

    Toshihiko Imamura

  4. Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan

    Kazuko Kudo

  5. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan

    Hiroshi Kawaguchi

  6. Division of Hematology/Oncology, Nagano Children’s Hospital, Azumino, Japan

    Kazuo Sakashita

  7. Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan

    Masahiro Yasui

  8. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yuhki Koga

  9. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan

    Ryoji Kobayashi

  10. Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan

    Eiichi Ishii

  11. National Center for Child Health and Development, Tokyo, Japan

    Junichiro Fujimoto

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

    Keizo Horibe

  13. Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan

    Fumio Bessho

  14. Department of Pediatrics and Adolescent Medicine, Juntendo University School of Medicine, Tokyo, Japan

    Yukiko Tsunematsu

  15. Department of Laboratory Medicine, Uji-Tokushukai Medical Center, Uji, Kyoto, Japan

    Shinsaku Imashuku

Authors
  1. Akira Morimoto
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  2. Yoko Shioda
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  3. Toshihiko Imamura
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  4. Kazuko Kudo
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  5. Hiroshi Kawaguchi
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  6. Kazuo Sakashita
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  7. Masahiro Yasui
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  8. Yuhki Koga
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  9. Ryoji Kobayashi
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  10. Eiichi Ishii
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  11. Junichiro Fujimoto
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  12. Keizo Horibe
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  13. Fumio Bessho
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  14. Yukiko Tsunematsu
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  15. Shinsaku Imashuku
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Corresponding author

Correspondence to Akira Morimoto.

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The authors have no conflicts of interest to declare.

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On behalf of the Japan LCH Study Group.

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Morimoto, A., Shioda, Y., Imamura, T. et al. Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study. Int J Hematol 104, 99–109 (2016). https://doi.org/10.1007/s12185-016-1993-3

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  • DOI: https://doi.org/10.1007/s12185-016-1993-3

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