Strategic Treatment Interruptions During Imatinib Treatment of Chronic Myelogenous Leukemia |
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Authors: | Dana Paquin Peter S Kim Peter P Lee Doron Levy |
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Institution: | 1.Department of Mathematics,California Polytechnic State University,San Luis Obispo,USA;2.Department of Mathematics,University of Utah,Salt Lake City,USA;3.Division of Hematology, Department of Medicine,Stanford University,Stanford,USA;4.Department of Mathematics and Center for Scientific Computation and Mathematical Modeling (CSCAMM),University of Maryland,College Park,USA |
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Abstract: | Although imatinib is an effective treatment for chronic myelogenous leukemia (CML), and nearly all patients treated with imatinib
attain some form of remission, imatinib does not completely eliminate leukemia. Moreover, if the imatinib treatment is stopped,
most patients eventually relapse (Cortes et al. in Clin. Cancer Res. 11:3425–3432, 2005). In Kim et al. (PLoS Comput. Biol. 4(6):e1000095, 2008), the authors presented a mathematical model for the dynamics of CML under imatinib treatment that incorporates the anti-leukemia
immune response. We use the mathematical model in Kim et al. (PLoS Comput. Biol. 4(6):e1000095, 2008) to study and numerically simulate strategic treatment interruptions as a potential therapeutic strategy for CML patients.
We present the results of numerous simulated treatment programs in which imatinib treatment is temporarily stopped to stimulate
and leverage the anti-leukemia immune response to combat CML. The simulations presented in this paper imply that treatment
programs that involve strategic treatment interruptions may prevent leukemia from relapsing and may prevent remission for
significantly longer than continuous imatinib treatment. Moreover, in many cases, strategic treatment interruptions may completely
eliminate leukemic cells from the body. Thus, strategic treatment interruptions may be a feasible clinical approach to enhancing
the effects of imatinib treatment for CML. We study the effects of both the timing and the duration of the treatment interruption
on the results of the treatment. We also present a sensitivity analysis of the results to the parameters in the mathematical
model. |
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