Improved outcome in the treatment of pediatric multifocal Langerhans cell histiocytosis - Results from the Japan Langerhans cell histiocytosis study group-96 protocol study

BACKGROUND. The treatment outcome of multifocal childhood Langerhans cell histiocyrosis (LCH) has not been satisfactory and has resulted in poor therapeutic responses with high mortality and a high incidence of reactivation with late sequelae. To overcome these issues, the Japan LCH Study Group-96 (JLSG-96) protocol was conducted prospectively from 1996 to 2001 in Japan. METHODS. Newly diagnosed children with multifocal LCH were classified into 2 groups: a single-system multisite (SS-m) group and a multisystem (MS) All patients initially were treated on Protocol A, which consisted of 6 weeks of induction therapy with combined cytosine arabinoside, vincristine (VCR), and prednisolone (PSL) followed by 6 months of maintenance therapy. Patients who had a poor response to the induction of Protocol A were switched to a salvage regimen (Protocol 13), which consisted of an intensive combination of doxorubicin, cyclophosphamide, VCR, and PSL. RESULTS. In total, 91 patients were treated, including 32 patients in the SS-m group and 59 patients in the MS group. At the median 5-year follow-up, 96.9% of patients in the SS-m group and 78.0% of patients in the MS group had good response status. Diabetes insipidus developed in 3.1% of patients in the SS-m group and in 8.9% of patients in the MS group. The overall survival rate at 5 years for the SS-m and MS groups was 100% and 94.4% +/- 3.2%, respectively. CONCLUSIONS. The JLSG-96 protocol attained very low mortality for pediatric patients with multifocal LCH.