Design of optimal disease and patient-specific chemotherapy protocols for the treatment of Acute Myeloid Leukaemia (AML)

摘要

The current project focuses on the design and optimization of chemotherapy protocols for Acute Myeloid Leukaemia (AML). AML is a type of blood cancer in which patients are characterized by a weakened blood and immune system due to abnormalities in the bone marrow where the tumour is located. In that respect, there is a high risk that the patient will not withstand the treatment due to life-threatening toxicities of the chemotherapeutic drug mix. Therefore the individualization and optimization of treatment dose and schedule is essential to balance the benefits of higher dose therapy against the tumour with the toxicity to normal tissue. This balance can be achieved by modelling key biological mechanisms as a means to gain insight into the effects of chemotherapy, which can then be used as a predictive tool for patient response during treatment (Dua, 2005; Dua,2008).In this work, we extend our previous model (Pefani et. al., 2011) for the first cycle of chemotherapy for the treatment of AML to include the chemotherapeutic drug action of both anticancer drugs used in current treatment protocols: cytarabine (Ara-C) and daunorubicin (DNR). The simulation and optimization results demonstrate the need for optimal treatment schedule in order to limit the life-threatening toxicities of chemotherapy-induced cytopenia in patients with AML undergoing treatment.