The effect of low dose Ara-C in acute nonlymphoblastic leukaemias and atypical leukaemia.

Nine patients with nonlymphocytic leukaemia and one patient with refractory anaemia with excess of blasts (RAEB) were treated subcutaneously with Ara-C at a low dose of 10 mg/m2/12 h; complete remission was obtained in seven patients. In all cases severe pancytopenia was observed during treatment. We measured the concentration of Ara-C in serum, and found that the maximum concentration reached a peak (52-132 ng/ml; mean 84.2 ng/ml) at 15 min following injection. These concentrations can be considered sufficient to inhibit DNA synthesis. Primary short-term culture of human leukaemic cells with low dose Ara-C was also performed, and differentiation of leukaemic cells was observed for several types of leukaemic cells. The in vitro findings corresponded to the observed clinical effects. From the above results, the action of low dose Ara-C may have resulted from a combination of two different mechanisms, its cytostatic effect and its differentiation-inducing effect.