The Computer Simulation of Leukemia Therapy

Combined Pharmacokinetics, Intracellular Enzyme Kinetics, and Cell Kinetics of the Treatment of L1210 Leukemia by Ara-C

by Thomas L. Lincoln, Paul F. Morrison, Jerry Aroesty, Grace M. Carter

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A comprehensive computer model of the chemotherapy of leukemia, as applied to a specific drug, cytosine arabinoside (ara-C), is described. This drug has already been instrumental in prolonging survival in adult leukemia, and suggestions are made in this report, on the basis of the simulations, for improving its clinical use. The basic model applies to any animal species; however, the detailed measurements for incorporation in the simulations described in this report apply only to L1210 leukemia and mice. The simulations thus involve experimental therapeutics, while the discussion relates the results to the potential improvement of clinical therapy. Individual computer-based mathematical models of cell growth, drug distribution, intracellular biochemistry, and cellular lethality are developed and individually tested based on relevant biological measurement and similitude. Once the component models have been verified, they are then integrated into a comprehensive model of treatment.

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