2-Chlorodeoxyadenosine (2-CDA) for the treatment of refractory or recurrent Langerhans cell histiocytosis (LCH) in pediatric patients.

BACKGROUND: Pediatric patients with Langerhans cell histiocytosis (LCH) may become refractory to conventional therapy or present with repeated recurrences over several years. Current therapeutic options such as prednisone, vinblastine, etoposide, and cyclosporine are associated with significant acute toxicities and late effects. Recent reports suggested that 2-chlorodeoxyadenosine (2-CDA) may be an effective agent in adults with LCH. The purpose of this study was to determine the safety and efficacy of 2-CDA in children with LCH.

METHODS: This report presents the data collected from the first three patients that have completed this trial. Patients were enrolled in a prospective study after informed consent was obtained. Patients had a confirmed diagnosis of LCH that had recurred several times or not responded to standard therapy. Patients were given a starting dose of 5 mg/M2 of daily continuous infusion for three days duration. Two patients had their dose increased to 6.5 mg/M2/ day. A total of 4-6 courses were given, and courses were repeated every 3-4 weeks. Thirteen of fifteen courses were given as outpatients at home.

RESULTS: Each patient completed therapy with myelosuppression the primary toxicity. Pt. 1 initially received a higher dose of 2-CDA and developed sepsis. The dose was reduced to current study levels and no other incidence of infection, fever, and neutropenia, or blood product transfusion was required. All three patients are free of active disease 10-18 months after completing 2-CDA.

CONCLUSION: Three patients with LCH refractory to standard therapy had CR to 2-CDA, given at 5-6.5 mg/M2/day for 3 days, without significant toxicity.