RESUMO
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.
Assuntos
Medula Óssea/efeitos dos fármacos , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Leucemia Monocítica Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Tioguanina/uso terapêutico , Adolescente , Adulto , Medula Óssea/patologia , Quimioterapia Combinada , Feminino , Humanos , Leucemia Monocítica Aguda/patologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico/efeitos dos fármacosRESUMO
The prognostic significance of the pretreatment growth characteristics of marrow blasts was examined in 37 patients with acute nonlymphocytic leukemia (ANLL) treated with a similar therapeutic regimen. Initial mitotic index (MI) and in vitro 3H-thymidine labeling index (LI) were broadly distributed showing no correlation to other initial variables, such as age or absolute blast count. No relationship whatsoever was observed between the pretreatment LI, MI and either the likelihood of achieving a complete remission or the remission and survival length. We conclude that the initial growth characteristics of marrow blasts do not play a significant role in predicting the therapeutic response in ANLL; age, modality of therapy and, possibly, the dynamic perturbations of the proliferative activity of the blast cells induced by treatment should be regarded as more reliable prognostic indicators in ANLL.