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
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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.
KeywordsLangerhans 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).
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Conflict of interest
The authors have no conflicts of interest to declare.
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