Arabinosyl Cytosine in Chronic Myeloid Leukaemia: Evidence for High Cytokinetic Sensitivity of Myeloblasts

Abstract

The effect of a single and repeated i.v. push dose(s) of arabinosyl cytosine (ARA-C) was investigated in 9 chronic myeloid leukemia (CML) patients in non-blastic phase. This was done by determining separately the relative compartment size, the mitotic index (IM) and the in vitro 3H-TdR labeling index (IL) of marrow and blood myeloblasts (MB) and promyelocytes plus myelocytes (PMC + MC), before and at intervals after the drug. After a single dose of ARA-C, the IL of marrow MB declined rapidly and recovered thereafter, often with an overshoot at 15 h. After 2 to 4 doses of ARA-C, the IL of marrow and blood MB rose by a factor of 2-3 and was maintained at a plateau during further treatment. The behavior of the IL of blood MB was not always the same as that of marrow MB. The IM of marrow MB did not rise proportionally to the IL and sometimes was decreased. These kinetic perturbations may reflect an accumulation of MB in S-phase where many but not all of them were trapped and sooner or later died. With a few exceptions, ARA-C induced only milder kinetic perturbations in marrow and blood PMC + MC. The overall results were in agreement with the generally accepted mechanism of action of ARA-C (S-phase specific effector agent), and with studies that indicated that the effect of ARA-C depended on the growth pattern and on the degree of maturation of the target cells. A proper evaluation of ARA-C on a cell population should take into account the existence of different cell pools, provided with different proliferative activity and potential and with variable degrees of maturation.