The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level >/=800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.