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Intensification of treatment with vinca alkaloid does not improve outcomes in pediatric patients with Langerhans cell histiocytosis: results from the JPLSG LCH-12 study

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Abstract

Chemotherapy with cytarabine, vincristine (VCR), and prednisolone has achieved low mortality rates in pediatric patients with Langerhans cell histiocytosis (LCH). However, relapse rates remain high, making event-free survival (EFS) rates unsatisfactory. A nationwide clinical trial, LCH-12, tested a modified protocol in which the early maintenance phase was intensified with increasing dosages of VCR. Patients newly diagnosed with multifocal bone (MFB) or multisystem (MS) LCH and aged < 20 years at diagnosis were enrolled between June 2012 and November 2017. Of the 150 eligible patients, 43 with MFB were treated for 30 weeks and 107 with MS LCH were treated for 54 weeks. One patient with MS LCH died of sepsis during the induction phase. The 3-year EFS rates among patients with MFB LCH, risk organ (RO)-negative MS LCH, and RO-positive MS LCH were 66.7% (95% confidential interval [CI], 56.5–77.0%), 66.1% (95% CI 52.9–76.4%), and 51.1% (95% CI 35.8–64.5%), respectively, similar to previously observed rates. EFS rates were significantly lower in patients with disease activity scores > 6 than in those with scores ≤ 6. The strategy that included more intense treatment with VCR was not effective. Other strategies are required to improve outcomes in patients with pediatric LCH.

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Data Availability

Due to ethical considerations, individual participant data will not be available.

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Acknowledgements

We thank all of the patients, their families, physicians and staff in the Japanese Paediatric Leukaemia/Lymphoma Study Group and Japan Children’s Cancer Group who contributed to this study.

Funding

This work was supported by the Ministry of Health, Labor, and Welfare, Japan (Grant number: Research on Measures for Intractable Disease H22-General-072, H24-General-076 and H26-General-068 to A. Morimoto) and the Japan Agency for Medical Research and Development, Japan (Grant number: 15ek0109055h0202 and 16ek0109055h0203 to A. Morimoto, and Grant 193 number: 20ck0106605h0001 to Y. Shioda).

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Authors and Affiliations

  1. Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan

    Akira Morimoto

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

    Yoko Shioda

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

    Kazuko Kudo

  4. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Hirokazu Kanegane

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

    Toshihiko Imamura

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

    Katsuyoshi Koh

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

    Yoshiyuki Kosaka

  8. Departments of Hematology/Oncology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Yuki Yuza

  9. Department of Clinical Research, Saitama Children’s Medical Center, Saitama, Japan

    Atsuko Nakazawa

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

    Akiko M. Saito

  11. Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin, Japan

    Tomoyuki Watanabe

  12. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    Yozo Nakazawa

  13. Department of Pediatrics, Showa Inan General Hospital, 3230, Akaho, Komagane, Nagano, 399-4117, Japan

    Akira Morimoto

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  1. Akira Morimoto
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  2. Yoko Shioda
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Correspondence to Akira Morimoto.

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12185_2023_3568_MOESM1_ESM.tif

Outcomes of patients in the trial treatment group. MFB, multifocal bone; MS, multisystem; RO, risk organ involvement; GR, good response; PR, partial response; NR, no response; PD, progressive disease; AD-p, active disease progression (TIF 322 KB)

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Morimoto, A., Shioda, Y., Kudo, K. et al. Intensification of treatment with vinca alkaloid does not improve outcomes in pediatric patients with Langerhans cell histiocytosis: results from the JPLSG LCH-12 study. Int J Hematol 118, 107–118 (2023). https://doi.org/10.1007/s12185-023-03568-0

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  • DOI: https://doi.org/10.1007/s12185-023-03568-0

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