Oral methotrexate and alternate-day prednisone for low-risk Langerhans cell histiocytosis

Many treatments for low-risk Langerhans cell histiocytosis (LCH) involve unpleasant side-effects or risks of late effects. To provide treatment with minimal toxicity and no known risk of late effects, we have used oral alternate-day prednisone (PDN, 40 mg/sq.m./day) and weekly methotrexate (MTX, 20 mg/sq.m. once weekly) in a series of 13 children with 17 episodes of LCH. Patients were monitored with monthly physical examinations, blood counts and chemistry panels, and radiographs and scans obtained at the treating physician's discretion. Patients who responded had the prednisone tapered and MTX discontinued after three months of treatment. Recurrences while treatment was being tapered, or after its discontinuation, were managed with resumption of MTX and PDN. Treatment was successful in 16 of the 17 episodes, meaning that symptoms resolved and abnormal physical or radiographic findings improved. Symptomatic relief occurred in two weeks or less in 14 of 17 episodes; objective improvement generally occurred within one month, and in all cases by three months. The median duration of treatment was 5 months. Toxicity was limited to slight, transient elevations in hepatic enzymes in three patients. We conclude that oral chemotherapy with alternate-day PDN and weekly MTX is effective and non-toxic in patients with low-risk LCH.