A mathematical model of human granulopoiesis to optimize growth factor scheduling during anti-cancer chemotherapy

Hematopoiesis is a tissue with high proliferative activity being responsible for peripheral blood cell production. The normal steady-state production can temporarily be impaired during the administration of anti-cancer therapies. In particular, the deficiency of neutrophil granulocytes (neutropenia) in the peripheral blood is of clinical importance, since patients are prone to potentially life-threatening infections. G-CSF is a hematopoietic growth factor which specifically stimulates granulopoietic cell production. Therefore, G-CSF is widely used in clinical practice to attenuate chemotherapy induced neutropenia. However, the timing of G-CSF administration is crucial for optimal attenuation.

In this talk, I will present a mathematical model of human granulopoiesis which is able to describe the blood neutrophil dynamics during chemotherapy and G-CSF administration. A set of concatenated compartments is used to describe the population kinetics of hematopoietic stem cells, granuloid precursors and mature blood neutrophils. The system is regulated by several feed-back loops. The model was used to systematically explore the impact of different G-CSF administration schedules on neutrophil population dynamics in order to identify optimal schedulings.