Immunological Effects After Stem Cell Transplants for Chronic Myeloid Leukemia Patients

Chronic Myeloid Leukemia (CML) is the best understood cancer, and nowadays one of the most successfully treated; its analysis can supply paradigms for analyzing more common, less well-characterized cancers. Our research will devise and calibrate a biologically motivated, quantitative model of graft vs leukemia immunological action following blood stem cell transplants from a healthy donor to a CML patient. Recently, many mathematical/computational cell population dynamics models have been developed to better understand CML and improve treatment. We will extend these models to recent data on how, after a transplant, lymphocytes from a donor’s immune system can help eliminate residual patient “leukemic stem cells” (i.e. primitive CML cells that can regenerate the entire diverse cancer cell population). Modeling will use a system of first-order nonlinear ordinary differential equations. The main difficulty will be calibrating the adjustable parameters in those equations. This study will give a better understanding of basic CML cell population dynamics by quantitatively relating transplant data to otherwise apparently unrelated data on other CML aspects, such as latency, response to modern treatment by tyrosine kinase inhibitors (e.g. imatinib), development of drug resistance, and/or progression to blast crisis. The results may help uncover possible improvements in CML transplant protocols. Moreover, insights may be gained into stem cell dynamics, treatment responses, and/or immune system interactions for other cancers.