P3.01 A Decision Tool for the Design of Optimal Personalised Chemotherapy Protocols for the Treatment of Acute Myeloid Leukaemia (AML)

Abstract

ABSTRACT AML is an aggressive cancer of the blood and bone marrow requiring intensive chemotherapy which, although effective for debulking tumour burden, is also highly destructive to normal tissues, often to a life-threatening extent. In current clinical practice only few patient-specific factors are taken into consideration and choice of treatment often depends on the treating physician's experience. However, there is a need for a systematic design of optimal protocols that account for both disease and patient characteristics. Towards this end, a framework is presented ( fig. 1 ) for the derivation of a Personalised-Chemotherapy Advisor (PC-Advisor) tool. The central part of this tool is a mathematical model that will enable the capture of patient behaviour under chemotherapy for a provided set of individual and disease parameters. In this work, a model is derived by combining the actions on the cell cycle, (drug target), with pharmacokinetic and pharmacodynamic aspects. Simulation and optimisation results are presented using this model for two patient case studies. The studied patients are of same sex, age and body mass index characteristics. However, their initial tumour burden and cell cycle times differ. They are both treated with the same treatment protocol in the model as they would be in clinical practice (a combination of cytarabine and daunorubicin). At completion of the first chemotherapy cycle one patient displays a bone marrow which contains a higher number of normal cells, whilst the other exhibits a higher number of AML cells. An optimisation problem is formulated thereafter for the latter patient resulting in the normal cell population incrementing enough to allow for normal bone marrow tissue recovery prior to the next chemotherapy cycle to further decrease AML cells. Model analysis results reveal the potential future applicability of the proposed tool and indicate the need for an interdisciplinary approach between clinicians, experimental- and model-based experts to collaborate in enabling personalised schedules for chemotherapy delivery in cancers such as AML. Download : Download full-size image Fig. 1 . Framework for the design of optimal personalised chemotherapy protocols.