In vitro exposure of leukemic cells to low concentration arabinosyl cytosine: No evidence of differentiation inducing activity

Low dose Arabinosyl Cytosine (LD ARA-C) is widely used for treatment of acute non-lymphocytic leukemia (ANLL) and myelodysplastic syndrome (MDS) in the elderly, based on a favorable response rate and on the hypothesis that LD ARA-C can induce differentiation or maturation of leukemic cells. We investigated the effect of low concentration of ARA-C on the growth of marrow cells that were obtained from 6 cases of MDS and from 11 cases of ANLL by using the in vitro culture system for normal granulo-monocyte precursors (CFU-GM). At ARA-C concentrations equal to or higher than 1 ng/ml cell growth was inhibited in a dose-dependent manner. At ARA-C concentration of 0.1 ng/ml cell growth was slightly affected, but colony number and colony cell composition were identical to control cultures. This experiment did not support the hypothesis that ARA-C can induce leukemic cells to recover any normal growth patterns but confirmed that even very low ARA-C concentrations can inhibit or slow down leukemic cell proliferation.