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Stability of a Gleevec and immune model with delays

Frédéric Mazenc 1 Peter S. Kim 2 Silviu-Iulian Niculescu 2
1 MERE - Water Resource Modeling
CRISAM - Inria Sophia Antipolis - Méditerranée , INRA - Institut National de la Recherche Agronomique : UMR0729
Abstract : This paper focuses on the stability analysis of a delay-differential system encountered in modeling immune dynamics during Gleevec treatment for chronic myelogenous leukemia. A simple algorithm is proposed for the analysis of delay effects on the stability. Such an algorithm takes advantage of the particular structure of the dynamical interconnections of the model. The analysis shows that the model yields three fixed points, two of which are always unstable and one of which is sometimes stable. The stable fixed point corresponds to an equilibrium solution in which the leukemia population is kept below the cytogenetic remission level. This result implies that, during Gleevec treatment, the resulting anti-leukemia immune response can serve to control the leukemia population. However, the rate of approach to the stable fixed point is very slow, indicating that the immune response is largely ineffective at driving the leukemia population towards the stable fixed point. To extend the stability analysis with respect to the delay parameter, we conduct a global nonlinear analysis to demonstrate the existence of unbounded solutions. We provide sufficient conditions based on initial cell concentrations that guarantee unbounded solutions and comment on how these conditions can serve to predict whether Gleevec treatment will result in a sustained remission based on a patient's initial leukemia load and initial anti-leukemia T cell concentration.
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Submitted on : Wednesday, September 4, 2013 - 10:03:35 AM
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Frédéric Mazenc, Peter S. Kim, Silviu-Iulian Niculescu. Stability of a Gleevec and immune model with delays. 47. IEEE Conference on decision and control, Dec 2008, Cancun, Mexico. pp.3317-3322, ⟨10.1109/CDC.2008.4738828⟩. ⟨hal-00857836⟩



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