Cell kinetics as related to treatment of patients with acute nonlymphoid leukemia

Much has been learned about normal and leukemic cell kinetics and the effect of drugs on the cell cycle by using classical kinetic techniques in patients with acute nonlymphoid leukemia (ANLL). It was found that in most cases leukemic cells proliferate slower than normal cells. Immature cells after division either died, entered into a resting state, or re-entered the cell cycle. However, classical kinetic features were inconclusive when used as predictors of prognosis. Most drug studies were done by measuring the percent of cells in various phases of the cell cycle from samples of bone marrow obtained before and after giving a drug or drug combination. All drugs used commonly in the treatment of ANLL, except 6-thioguanine, were evaluated singly and some in combination. Some phase of the cell cycle was affected by all of the drugs in most patients. The percent of cells arrested and the time of greatest response varied with the dose. When the kinetic studies were done after giving drugs sequentially, the location of effect and the length of the effect were the same as that seen when the drugs were given singly. More studies are needed using known principles of cell kinetics and bone marrow culture technology. More information about leukemic stem cells can be learned, subsets of patients with ANLL may be more clearly defined, and new treatment protocols may be designed.