High-dose cytosine arabinoside in acute myeloid leukemia : rationale and results

Experimental models have demonstrated that a small increase in drug dose results in an extremely large increase in leukemia cell kill, thus establishing a rationale for the use of high doses of chemotherapy in clinical practice. Cytosine arabinoside (Ara-C) has been the most extensively evaluated drug in dose-intensive regimens in the setting of adults with acute myeloid leukemia. While as yet there is no apparent evidence that an intensification of Ara-C during induction can be beneficial in this category of patients, the use of high-dose Ara-C (HIDAC) in the post-remission phase is one of the greatest achievements of modern oncology. In individuals less than 60 years of age with AML and a favorable karyotype, HIDAC-based consolidation has resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Since new cytotoxic agents have recently expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy to optimize schedules and combinations of HIDAC in combination with other drugs in patients with AML are warranted.