International Journal of Hematology

, Volume 108, Issue 2, pp 192–198 | Cite as

Intensification of induction therapy and prolongation of maintenance therapy did not improve the outcome of pediatric Langerhans cell histiocytosis with single-system multifocal bone lesions: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study

  • Akira MorimotoEmail author
  • Yoko Shioda
  • Toshihiko Imamura
  • Kazuko Kudo
  • Toshiyuki Kitoh
  • Hiroshi Kawaguchi
  • Hiroaki Goto
  • Yoshiyuki Kosaka
  • Yukiko Tsunematsu
  • Shinsaku Imashuku
  • On behalf of the Japan LCH Study Group
Original Article


Langerhans cell histiocytosis (LCH) with single-system (SS) multifocal bone (MFB) lesions is rarely fatal, but patients may experience relapses and develop LCH-associated sequelae. To evaluate effect on outcomes of pediatric multifocal LCH, we tested a treatment protocol modified from the Japan Langerhans Cell Histiocytosis Study Group (JLSG)-96 study. We assessed the outcomes of all consecutive newly diagnosed pediatric patients with LCH with SS-MFB lesions who were treated with JLSG-02 protocol in 2002–2009. JLSG-02 was modified from JLSG-96 as follows: increased prednisolone dosage at the induction phase and extension of maintenance therapy duration from 24 to 48 weeks. In total, 82 patients with a median follow-up duration of 8.0 years were eligible for analysis. At 6 weeks, 92.7% responded to induction; however, 27.6% of responders experienced relapses. In total, 4.8% developed central nervous system-related sequelae, including central diabetes insipidus and neurodegeneration, which were associated with relapse. None of the patients died. The 5-year event-free survival rates were not different between JLSG-02 and -96 cohort (66.7 vs. 65.1%; p = 0.697). Modification of previous treatment protocol did not contribute to improvement of outcomes in LCH with SS-MFB lesions.


Langerhans cell Histiocytosis Multifocal bone disease Chemotherapy Central diabetes insipidus Neurodegeneration 



The authors thank all physicians who participated in the JLSG-02 study. We also thank Ms. Yasuko Hashimoto for secretarial assistance. This work was supported by the Ministry of Health, Labor, and Welfare, Japan (Grant number: Research on Measures for Intractable Disease H24-General-076 and H-26-General-068) and the Japan Agency for Medical Research and Development (Grant number: 15ek0109055h0202 and 16ek0109055h0203).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.


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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Akira Morimoto
    • 1
    Email author
  • Yoko Shioda
    • 2
  • Toshihiko Imamura
    • 3
  • Kazuko Kudo
    • 4
  • Toshiyuki Kitoh
    • 5
  • Hiroshi Kawaguchi
    • 6
  • Hiroaki Goto
    • 7
  • Yoshiyuki Kosaka
    • 8
  • Yukiko Tsunematsu
    • 9
  • Shinsaku Imashuku
    • 10
  • On behalf of the Japan LCH Study Group
  1. 1.Department of PediatricsJichi Medical UniversityShimotsukeJapan
  2. 2.Pediatric Cancer CenterNational Center for Child Health and DevelopmentTokyoJapan
  3. 3.Department of PediatricsKyoto Prefectural University of Medicine, Graduate School of Medical ScienceKyotoJapan
  4. 4.Department of PediatricsFujita Health University School of MedicineToyoakeJapan
  5. 5.Laboratory of PediatricsAichi Gakuin University School of PharmacyNagoyaJapan
  6. 6.Department of PediatricsHiroshima University Graduate School of Biomedical and Health SciencesHiroshimaJapan
  7. 7.Division of Hematology/OncologyKanagawa Children’s Medical CenterYokohamaJapan
  8. 8.Department of Hematology and Oncology, Children’s Cancer CenterHyogo Prefectural Kobe Children’s HospitalKobeJapan
  9. 9.Department of Pediatrics and Adolescent MedicineJuntendo University School of MedicineTokyoJapan
  10. 10.Department of Laboratory MedicineUji-Tokushukai Medical CenterUjiJapan

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