A model for the chemotherapy of acute leukemia with 1-beta-D-arabinofuranosylcytosine.

The pharmacology of cytosine arabinoside (1-β-d-arabinofuranosylcytosine) is reviewed and integrated with data on the cell kinetics of normal hematopoietic and leukemic stem cells to form a model for the chemotherapy of acute leukemia. The objective of the model is to produce, by using optimal scheduling and optimal drug levels of cytosine arabinoside, a complete eradication of the leukemic stem cells during a single course of therapy by chemotherapeutic exploitation of the potential differences in the growth fraction of the leukemic and normal stem cells. The use of nutritional factors to increase the growth fraction of the leukemic stem cells is discussed in the model. Preliminary results on the effect of the model on the survival of leukemic blast cells in a patient with acute myeloblastic leukemia are reported. The use of the model to estimate the cell cycle parameters of leukemic stem cells is discussed.