A. Nikitich, O. Demin Jr, O. Demin; Institute for Systems Biology Moscow, Moscow, Russian Federation

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a form of cancer of the white blood cells, characterized by the overproduction of immature white blood cells. About 80% of ALL patients will have complete remission, but the question about the most effective therapy remains open. The aim of this work was to reproduce the dynamics of ALL progression and compare efficiency of several clinically accepted and potential treatments.
METHODS: A system of differential equations describing B-lymphoblasts cell cycle, PK of several compounds (PEG-L-asparaginase, sorafenib), ALL progression for adults and children during treatment and without it was developed. Model parameters were calculated/fitted using literature data.
RESULTS: Model satisfactorily reproduces in vitro data on B-lymphoblasts cell lines proliferation and distribution between cell cycle phases with and without drug administration, and in vivo blasts levels in blood measured during ALL progression. Model predicts that patients with slow rate of ALL progression have better respond to treatment.
CONCLUSION: Systems pharmacology model of ALL progression and treatment is a good tool to compare different clinically accepted and potential therapies. Also, model allows to describe different sub-populations of ALL patients (adults vs. children; highly vs. low proliferative).