Abstract 865
Hematology-Oncology I Platform, Saturday, 5/1
The treatment of multisystem Langerhans cell histiocytosis (LCH) is controversial and ranges from mild to intensive chemotherapy. The purpose of this study was to compare, for the first time in a controlled and randomized manner, the efficacy of two commonly used single agents, vinblastine and etoposide. 148 previously untreated patients with multisystem LCH were randomized to receive a 24 week course of either vinblastine (6 mg/m2 i.v. weekly) or etoposide (150 mg/m2/d iv for 3 consecutive days every 3 weeks), together with an initial pulse of corticosteroids. Response was assessed at regular intervals according to uniform criteria. 143 patients (95%) were evaluable (72 females and 71 males; median age 18 months, range: birth - 14 years, 5 months; median observation time: 4 years, 11 months). Treatment with vinblastine (74 patients) or etoposide (69 patients) was equivalent with respect to rapid (6 weeks) response (57% and 49%, p=0.37), overall response (58% and 65%, p=0.38), and toxicity (47% and 58%, p=0.20). Likewise, the probability of survival (76% and 80%, p=0.40), disease reactivation (61% and 55%, p=0.67), and development of permanent consequences (39% and 51%, p=0.97) including diabetes insipidus (22% and 23%, p=0.93) were not significantly different. Overall, 100/143 patients (70%) became free of disease within a median of 6 months from the start of treatment. While 50 patients experienced a reactivation of LCH, it was usually mild. Toxicity was mild to moderate and comparable in both treatment arms. All children ≥ 2 years old without involvement of any risk organ at diagnosis, i.e. liver, lungs, hematopoietic system, or spleen, survived. In children with risk organ involvement at diagnosis, lack of response after a very short (6 week) initial treatment was identified as a new prognostic indicator, predicting a high (60%) mortality rate. We conclude that vinblastine and etoposide are equally effective single agents in the treatment of multisystem LCH, but that in some patients more intensive therapy may be necessary to improve outcome.
