Arabinosyl cytosine in chronic myeloid leukaemia: evidence for high cytokinetic sensitivity of myeloblasts.
The effect of a single and of repeated i.v. push dose(s) of Arabinosyl Cytosine (ARA-C) has been investigated in 9 chronic myeloid leukaemia (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 labelling 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 declines rapidly, and recovers thereafter, often with an overshoot at 15 h. After 2 to 4 doses of ARA-C, the IL of marrow and blood MB rises by a factor of 2 to 3, and is maintained at a plateau during further treatment. The behaviour of the IL of blood MB is not always the same as that of marrow MB. The IM of marrow MB does not rise proportionally to the IL, and sometimes is even found to be decreased. It is suggested that these kinetic perturbations reflect an accumulation of MB in S-phase where many but not all of them are trapped and sooner or later die off. With a few exceptions, ARA-C induces only milder kinetic perturbations in marrow and blood PMC+MC. The overall results of this study are in agreement with the generally accepted mechanism of action of ARA-C (S-phase specific effector agent), and with studies that indicate that the effect of ARA-C depends on the growth pattern and on the degree of maturation of the target cells. It is suggested that 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.
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D013997:Time Factors
D004273:DNA, Neoplasm; D003561:Cytarabine