APPLICATION OF SYSTEMS PHARMACOLOGY MODELING FOR EVALUATION OF THERAPIES EFFECT ON BLAST DYNAMICS IN ACUTE LYMPHOBLASTIC LEUKEMIA
Author(s): ,
Antonina Nikitich
Affiliations:
Institute for Systems Biology Moscow,Moscow,Russian Federation
Oleg Demin Jr
Affiliations:
Institute for Systems Biology Moscow,Moscow,Russian Federation
(Abstract release date: 05/21/15) EHA Library. Nikitich A. 06/12/15; 99776; E878 Disclosure(s): Institute for Systems Biology Moscow
Mrs. Antonina Nikitich
Mrs. Antonina Nikitich
Contributions
Abstract
Abstract: E878

Type: Eposter Presentation

Background
Acute lymphoblastic leukemia (ALL) is an acute form of cancer of the white blood cells, characterized by the overproduction of cancerous, immature white blood cells. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. About 80% of ALL patients will have complete remission, but the question about the most effective therapy remains open. 

Aims
The aim of this work is to reproduce dynamics of ALL progression and compare efficacy of several clinically accepted and potential treatments.

Methods
Systems pharmacology model of ALL progression and treatment was developed. The model is a system of ordinary differential equations. It includes description of B-lymphoblasts proliferation and distribution between cell cycle phases with and without treatment, B-lymphoblasts and other blood cells dynamics during ALL progression, pharmacokinetics of several compounds (vorinostat, sorafenib) and its effect on B-lymphoblasts dynamics in ALL patients. Parameters of the model were calculated on the basis of the literature data or fitted against published experimental data. Treatment was simulated for two types of virtual patients: with slow and high rate of disease progression.

Results
Model satisfactory reproduces in vitro data on B-lymphoblasts cell lines proliferation and distribution between cell cycle phases with and without drug treatment and in vivo blasts levels in blood measured during ALL progression. The model was validated against blast dynamics during treatment with sorafenib. Model shows that for virtual patients with slow ALL progression vorinostat is more effective than sorafenib. For virtual patient with fast ALL progression both compounds are ineffective.

Summary
Model predicts that slow progression rate patients have better respond to the therapy. Systems pharmacology model of ALL progression and treatment could be used as a tool to compare different clinically accepted and potential treatments. 

Keyword(s): B cell acute lymphoblastic leukemia



Session topic: E-poster
Abstract: E878

Type: Eposter Presentation

Background
Acute lymphoblastic leukemia (ALL) is an acute form of cancer of the white blood cells, characterized by the overproduction of cancerous, immature white blood cells. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. About 80% of ALL patients will have complete remission, but the question about the most effective therapy remains open. 

Aims
The aim of this work is to reproduce dynamics of ALL progression and compare efficacy of several clinically accepted and potential treatments.

Methods
Systems pharmacology model of ALL progression and treatment was developed. The model is a system of ordinary differential equations. It includes description of B-lymphoblasts proliferation and distribution between cell cycle phases with and without treatment, B-lymphoblasts and other blood cells dynamics during ALL progression, pharmacokinetics of several compounds (vorinostat, sorafenib) and its effect on B-lymphoblasts dynamics in ALL patients. Parameters of the model were calculated on the basis of the literature data or fitted against published experimental data. Treatment was simulated for two types of virtual patients: with slow and high rate of disease progression.

Results
Model satisfactory reproduces in vitro data on B-lymphoblasts cell lines proliferation and distribution between cell cycle phases with and without drug treatment and in vivo blasts levels in blood measured during ALL progression. The model was validated against blast dynamics during treatment with sorafenib. Model shows that for virtual patients with slow ALL progression vorinostat is more effective than sorafenib. For virtual patient with fast ALL progression both compounds are ineffective.

Summary
Model predicts that slow progression rate patients have better respond to the therapy. Systems pharmacology model of ALL progression and treatment could be used as a tool to compare different clinically accepted and potential treatments. 

Keyword(s): B cell acute lymphoblastic leukemia



Session topic: E-poster

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