Drug-induced kinetic perturbations of the marrow blasts in acute leukemia. Effects of the daunorubicin, cytosine arabinoside and 6-thioguanine combination.
Cell kinetic changes induced in the marrow blasts by treatment with a triple cytotoxic regimen including daunorubicin, cytosine arabinoside and 6-thioguanine (DAT) were investigated in 6 previously untreated acute nonlymphocytic leukemia patients. A decrease in the labeling and mitotic indices was consistently observed 24 h after administration of daunorubicin, suggesting a G2 block and a preferential lytic effect on the S-phase cells operated by the drug. Conversely, cytosine arabinoside and 6-thioguanine in combination induced a series of kinetic perturbations variable from case to case; however, three principal patterns of kinetic response were recogized and discussed in detail. Useful information for the planning of a more rational antileukemic therapy can be drawn from a systematic study of the kinetic effects induced by drug combinations.
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D003561:Cytarabine / Q000627:therapeutic use*; D003630:Daunorubicin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index / Q000187:drug effects; D013866:Thioguanine / Q000627:therapeutic use*
D003561:Cytarabine; D013866:Thioguanine; D003630:Daunorubicin