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

Int J Hematol. 2018 Aug;108(2):192-198. doi: 10.1007/s12185-018-2444-0. Epub 2018 Mar 28.

Abstract

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.

Keywords: Central diabetes insipidus; Chemotherapy; Langerhans cell Histiocytosis; Multifocal bone disease; Neurodegeneration.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Insipidus / etiology
  • Female
  • Follow-Up Studies
  • Histiocytosis, Langerhans-Cell / complications
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / mortality
  • Humans
  • Induction Chemotherapy / methods*
  • Infant
  • Maintenance Chemotherapy / methods*
  • Male
  • Neurodegenerative Diseases / etiology
  • Prednisolone / administration & dosage*
  • Recurrence
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Prednisolone