Clinical use of clofarabine for adults and children with leukemia

Clofarabine is a second-generation nucleoside analogue designed to be more effective than precursor nucleoside analogues such as fludarabine and cladribine. Early clinical studies of clofarabine demonstrated its activity in hematologic malignancies, and clofarabine was approved by the United States Food and Drug Administration (FDA) for the treatment of relapsed and refractory pediatric acute lymphoblastic leukemia (ALL) in 2004. Clofarabine has significant efficacy in adults and children with hematologic malignancies including ALL, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). The unique biochemical modulation properties of clofarabine when used in combination with other established antileukemic drugs also make it an appealing agent for use in combination therapy with purine nucleoside analogues or DNA-damaging agents; these combinations have been tested in a number of studies in patients with ALL or AML. In this chapter, we review the development of clofarabine, the rationale and history of its use in combination regimens, and the potential roles and toxicities of these regimens in the treatment of adult and pediatric leukemias. The use of clofarabine in conditioning regimens prior to stem cell transplantation and for histiocytosis is also discussed.