Pharmacokinetic-pharmacodynamic modeling of maintenance therapy for childhood acute lymphoblastic leukemia.

ABSTRACT: In the treatment of childhood acute lymphoblastic leukemia (ALL), current protocols combine initial high-dose multiagent chemotherapy with prolonged oral therapy with 6-mercaptopurine (6MP) and low-dose methotrexate (MTX) maintenance therapy. Decades of research on ALL treatment have resulted in survival rates of approximately 90%. However, dose-response relationships vary widely between patients and insight into the influencing factors, that would allow for improved personalized treatment management, is insufficient. We use a detailed data set with measurements of thioguanine nucleotides and MTX in red blood cells and absolute neutrophil count (ANC) to develop pharmacokinetic models for 6MP and MTX, as well as a pharmacokinetic-pharmacodynamic (PKPD) model capable of predicting individual

SUBMITTER: Gebhard A 

PROVIDER: S-EPMC10359452 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature