OPTIMAL CONTROL APPLIED TO A GENERALIZED MICHAELIS-MENTEN MODEL OF CML THERAPY.

We generalize a previously-studied model for chronic myeloid leu-kemia (CML) [13,10] by incorporating a differential equation which has a Michaelis-Menten model as the steady-state solution to the dynamics. We use this more general non-steady-state formulation to represent the effects of various therapies on patients with CML and apply optimal control to compute regimens with the best outcomes. The advantage of using this more general differential equation formulation is to reduce nonlinearities in the model, which enables an analysis of the optimal control problem using Lie-algebraic computations. We show both the theoretical analysis for the problem and give graphs that represent numerically-computed optimal combination regimens for treating the disease. [ABSTRACT FROM AUTHOR]