Strategic Treatment Interruptions During Imatinib Treatment of Chronic Myelogenous Leukemia
- 126 Downloads
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.
KeywordsChronic myelogenous leukemia Imatinib Mathematical model Strategic treatment interruptions
Unable to display preview. Download preview PDF.
- Maserati, R., Foli, A., Tomasoni, L., Sighinolfi, L., Maggiolo, F., Sacchini, D., DiPietro, M., Bertelli, D., Tinelli, C., & Lori, F. (2007). Effects of structured treatment interruptions on metabolic anthropometric, immunologic, and quality of life outcomes in HIV-positive adults on HAART. Curr. HIV Res., 5(3), 337–343. CrossRefGoogle Scholar
- Mahon, F., Rea, D., Guilhot, F., Legros, L., Guilhot, J., Aton, E., Dulucq, S., Reiffers, J., & Rousselot, P. (2009). Persistence of complete molecular remission in chronic myeloid leukemia after imatinib discontinuation: interim analysis of the STIM trial. J. Clin. Oncol., 27, 7084. Google Scholar
- Piazza, R., Magistroni, V., Franceschino, A., Andreoni, F., Tornaghi, L. et al. (2006). The achievement of durable complete cytogenetic remission in late chronic and accelerated phase patients with CML treated with imatinib mesylate predicts for prolonged response at 6 years. Blood Cells Mol. Dis. 37, 111–115. CrossRefGoogle Scholar