These simulations indicate the plasma concentrations (median, 25-75th percentiles, and 1st-99th percentiles) expected for patients with observed MTX PK parameters derived from either the St. Jude Children’s
Research Hospital TOTAL XV frontline pediatric ALL study or the St. Jude Children’s Research Hospital MIOS, OS86, OS91, and OS2008 osteosarcoma studies. The frontline pediatric ALL study included 485 patients
(age 1 to 19 years old) with normal MTX excretion patterns and doses of MTX ranging from 0.5 to 8.2 g/m2 infused over 24 hours. The osteosarcoma studies included 172 patients (age 3 to 24 years old) with normal
MTX excretion patterns and a MTX dose of 12 g/m2 infused over 4 hours. These studies were performed in a center with real-time PK monitoring and adjustments in hydration and alkalinization were made as clinically
Less aggressive hydration, alkalinization, and lack of real-time monitoring might produce plasma MTX concentrations above those estimated in these graphs. In addition, each MTX treatment regimen may differ in
recommended thresholds for leucovorin rescue, and thresholds for clinical action should not be inferred from the data presented.