Pilot study to estimate the safety and effectiveness of hydroxyurea and methotrexate recurrent langerhans cell histiocytosis (LCH-HU-pilot)

Langerhans cell histiocytosis (LCH) is the most frequent type of histiocytosis and is characterized by both “inflammation/immune dysregulation” and “neoplastic disorder.” Although overall survival has remarkably improved through consecutive previous studies, the relapse-free survival rate is still only 60% to 70%, even in the latest clinical trials. Relapse of LCH is the most significant risk factor for permanent consequences in the central nervous system, such as diabetes insipidus, anterior pituitary hormone deficiency, and neurodegenerative diseases. In this trial, we evaluated the safety and effectiveness of hydroxyurea and methotrexate in recurrent LCH. Treatments in this study consisted of only orally administered drugs and not intravascularly administered drugs. Hydroxyurea therapy for patients with LCH is expected to be safer, less painful, and more cost-effective than other treatments for LCH. The results of this study could provide new therapeutic alternatives for recurrent LCH. METHODS AND ANALYSIS: This study was a non-blinded, multicenter, single-arm study. Recurrent (relapsed) LCH is defined as the appearance of new lesions or the enlargement of preexisting lesions due to LCH. In this study, all patients received hydroxyurea, and if the treatment response was unsatisfactory, methotrexate was added. The duration of treatment was 48 weeks. The primary endpoint was the rate of non-active disease achievement, which was 24 weeks after initiating hydroxyurea administration. No active disease is defined as the resolution of all the signs and symptoms related to LCH.