Harned and Gaynon pediatric ALL were durable and allowed some patients to successfully proceed to transplantation. Clofarabine has been approved by the FDA for the treatment of pediatric patients with relapsed or refractory ALL after at least 2 prior therapeutic regimens based on the induction of com- plete responses. Over the past decade, clofarabine has been the only anti-cancer agent to receive primary indication for use in children. Rational combinations of clofarabine with other active agents in refractory leukemias are currently under investi- gation. The early results of the phase I study of clofarabine in combination with cyclophosphamide and etoposide in pediatric patients with relapsed or refractory ALL or AML indicate that this combination shows significant activity in children with both subtypes of refractory leu- kemia and is well tolerated (Hijiya et al 2007). Pediatric studies of clofarabine in combination with cytarabine to enhance intracellular Ara-C triphosphate accumulation are also in progress. Such rationally designed combinations of clofarabine with standard agents may have a role in frontline therapy for newly diagnosed patients with higher risk disease. As of September, 2007 COG plans to study clofarabine-based combinations in a randomized phase III trial in patients with “very high risk” B-precursor ALL, ie, hypodiploidy, higher end-induction MRD, and/or induction failure. The proposed study tests a clofarabine blocks against the cyclophophamide/ara-c/thiopurine blocks that occupy 3 of the first 6 months of post-induction intensification. Plans in AML await completion of the current COG trials, AAML0523. Disclosures TMH has no conﬂicts of interest. PSG is on the speakers’ bureaus for Genzyme, Sanoﬁ-Aventis, and Enzon. References Aladjidi N, Auvrignon A, Leblanc T, et al. 2003. 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