Low dose cytosine arabinoside: partial remission of acute myeloid leukaemia without evidence of differentiation induction

Abstract

Thirteen patients with acute myeloid leukaemia aged from 19 to 81 were treated with low dose cytosine arabinoside (ARA-C) in a dose of 10-15 mg/m2 twice daily subcutaneously. Three complete remissions were obtained. Partial responses were observed in a further two patients. To analyse the action of low dose ARA-C freshly isolated leukaemic cells and cells from the cloned promyelocytic leukaemia cell line (HL60) were cultured in vitro in the presence of cytosine arabinoside. Minimal evidence of differentiation induction was observed when compared with the cytotoxic effects of the drug. These results suggest that ARA-C does not exert its anti-leukaemic effects by halting proliferation through differentiation induction. Rather, it appeared that the capacity of this agent to kill cells in S-phase produced a progressive depletion of the cycling leukaemic cells. This resulted in a corresponding steady decline in the total leukaemic cell population.