Low-dose ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes: a review of 20 years' experience.

Abstract

OR ALMOST 20 YEARS, cytosine arabinoside (ara-C) at both conventional doses (100 to 200 mg/m2/d x 5 to 10 days) or high doses (3 gm/m2 every 12 hours x 6 to 12 doses) has been the most active chemotherapy agent for the treatment of patients with acute nonlymphocytic leukemia (ANLL).lm4 In 1968, the Acute Leukemia Group B reported that low doses of ara-C (LD ara-C) (10 to 30 mg/m2/d) induced complete responses (CR) in a substantial proportion of patients.’ Nevertheless, since greater myelosuppression was observed with 50 to 100 mg/m2, the less intensive regimens were abandoned. A decade later a resurgence of interest in LDara-C (10 to 20 mg/m*/d) was stimulated by the description by Baccarani and Tura of the use of LDara-C in patients with ANLL’ and, subsequently by Wisch et al, in myelodysplastic syndrome (MDS).6 However, the hypothesis was that LDara-C might have a role as a differentiating agent, rather than as a cytotoxic. The rationale for this was, first, that both ANLL and MDS are presumed disorders of cellular maturation.7.8 Second, low levels of ara-C are capable of inducing histologic and functional differentiation of HL-60 cells, a human acute promyelocytic leukemia cell line.’ Third, LDara-C can be administered subcutaneously, permitting outpatient treatment. In addition, since conventional dose ara-C has predictable and tolerable toxicity, LDara-C should be associated with even less toxicity, possibly improving the therapeutic index. Finally, since a number of preliminary reports suggested clinical efficacy of LDara-C, this treatment might be of particular value in elderly patients with ANLL or MDS. Nevertheless, despite a large number of reports, the use of LDara-C remains extremely