An Extended Personalised Chemotherapy Response Model Incorporating Inflammation and Individual Variability in Childhood Acute Lymphoblastic Leukemia

Abstract

This study aims to develop a personalised pharmacokinetic / pharmacodynamic model for 6-mercaptopurine (6-MP) used in the treatment of childhood acute lymphoblastic leukemia (ALL). The developed model considers both neutrophil count and white blood cells in the context of lifestyle-related inflammatory responses (affected by nutrition, diet, and the vitamin D), genetic variations (e.g., TPMT), and also age-related pharmacokinetic values. In detail, the model is structured by equations corresponding absorption of 6-MP in the body, its metabolites (6-TGN, 6-mMPN, 6-TU), and also suppressive effects of the metabolites over the hematopoietic system. One unique aspect of the study is that the inflammatory response is integrated into the system as an additional component evaluating the lifestyle impact on hematopoietic production. The study confirms the model by running simulations for the patient profiles with different ages, genetic factors, and inflammatory conditions. The findings reveal leukocyte responses and ensure a basis for personalised dose optimisation.