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The Effects of Chemotherapy on the Kinetics of Leukemic Cell Behavior

Kettering-Meyer Laboratory (Affiliated with Sloan-Kettering Institute), Southern Research Institute, Birmingham, Alabama

In order to "cure" experimental leukemia in mice, it is necessary to kill every leukemic cell in the host (regardless of the total number, their anatomic distribution, or metabolic heterogeneity) with drug levels and schedules tolerated by the host.

The major stumbling blocks or obstacles appear to be associated with killing the relatively small but persistent fraction of leukemic cells which survive maximum tolerated therapy because of (a) lack of drugs with sufficient therapeutic index (hence, the problem of constant fractional survival of drug-sensitive cells in spite of continuous daily treatment); (b) the anatomical compartment problem, e.g., central nervous system; and (c) the drug resistance problem (drug selection of true variants). Results supporting these concepts and emphasizing the importance of (a) above are presented and discussed.