A randomized trial of treatment for multisystem Langerhans' cell histiocytosis

Objective: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. Study design: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m², given intravenously every week) or etoposide (150 mg/m²/d, given intravenously for 3 days every 3 weeks), and a single initial close of corticosteroids. Results: Vinblastine and etoposide were equivalent (P ≥ .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 80%), of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children ≥2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. Conclusions: Vinblastine and etoposide, with one close of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.