Background. Recent mathematical models have been developed to study the dynamics of chronic myelogenous leukemia (CML) under imatinib treatment. None of these models incorporates the anti-leukemia immune response. Recent experimental data show that imatinib treatment may promote the development of anti-leukemia immune responses as patients enter remission [Chen2007].
Methodology/Principal Findings. Using these experimental data we develop a mathematical model to gain insights into the dynamics and potential impact of the resulting anti-leukemia immune response on CML. We model the immune response using a system of delay differential equations, where the delay term accounts for the duration of cell division. The mathematical model suggests that anti-leukemia T cell responses may play a critical role in maintaining CML patients in remission under imatinib therapy. Furthermore, it proposes a novel concept of an 'optimal load zone' for leukemic cells in which the anti-leukemia immune response is most effective. Imatinib therapy may drive leukemic cell populations to enter and fall below this optimal load zone too rapidly to sustain the anti leukemia T cell response. As a potential therapeutic strategy, the model shows that vaccination approaches in combination with imatinib therapy may optimally sustain the anti-leukemia T cell response to potentially eradicate residual leukemic cells for a durable cure of CML.
Conclusions/Significance. The approach presented in this paper accounts for the role of the anti-leukemia specific immune response in the dynamics of CML. By combining experimental data and mathematical models we demonstrate that persistence of anti-leukemia T cells even at low levels seems to prevent the leukemia from relapsing (for at least 50 months). Consequently, we hypothesize that anti-leukemia T cells responses may help maintain remission under imatinib therapy. The mathematical model together with the experimental data of [Chen,2007] imply that there may be a feasible, low risk, clinical approach to enhancing the effects of imatinib treatment.