Cytokinetic changes after cytosine arabinoside in acute non-lymphocytic leukemia

Abstract

Changes in the S-phase compartment of blasts were measured after intravenous push-injections of cytosine-arabinoside (Ara-C, 100 mg/m 2, 380 mg/m 2 or 1000 mg/m 2 body surface) in 11 patients with acute non-lymphocytic leukemia. At several intervals after Ara-C injection blood and bone marrow samples were taken for autoradiography, DNA-flowcytometry and 3H-thymidine incorporation. The data obtained from the bone marrow aspirates were corrected for peripheral blood admixture. In untreated patients the three methods correlated very well. The perturbation of the cell-cycle after Ara-C administration shows for each method a specific pattern. Labelling indices reached, after an initial decrease, pretreatment levels at about 24 h after injection. Recruitment of cells into the cycling compartment could not be demonstrated. DNA-flowcytometry reveals a significant increase in the percentage of cells with > 2 n < 4 n DNA, with a maximum after about 30h. The discrepancy between autoradiography and DNA-flowcytometry after Ara-C injection may be due to the presence of cells arrested in S-phase. 3H-thymidine incorporation increased after an initial inhibition to about twice pretreatment values at 30 to 40 h after injection. This observation suggests partial synchronization. Incorporation of 3H-thymidine in peripheral nucleated cells correlated well with the corrected values of 3H-thymidine incorporation in the bone marrow. The perturbation of the cell-cycle appeared identical in the three different dosages used. The observations suggest that 24 h scheduling might be optimal for Ara-C given by push-injections.