The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients

Background: High-dose methotrexate (HD-MTX) is widely used as a standard chemotherapeutic agent in pediatric cancers. Most research studies have confirmed the therapeutic efficacy of HD-MTX; however, strategies to prevent side effects vary among institutions, especially in developing countries, with limited monitoring of plasma methotrexate level. Objective: To evaluate the effect of intravenous hydration during HD-MTX administration on plasma methotrexate clearance in pediatric oncology patients. Materials and methods: This study retrospectively reviewed 165 courses of HD-MTX administered to children with acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), or osteosarcoma. Demographic data of patients were collected. Adverse complications related to HD-MTX and 72-hour plasma methotrexate level were analyzed between patients receiving intravenous hydration >= 3,000 mL/m(2)/day and those receiving hydration <3,000 mL/m(2)/day. Results: Among 56 HD-MTX (1.5 g/m(2)) courses in ALL, delayed methotrexate clearance was only found in one course administered with hydration <3,000 mL/m(2)/day. However, no correlation was observed between adverse complications and methotrexate levels. Of 34 HD-MTX (1.5-3 g/m(2)) courses in NHL, no significant correlation was observed between methotrexate levels and intravenous hydration. However, increased adverse complications were found in the course with delayed methotrexate clearance. Interestingly, among 75 HD-MTX (10-12g/m(2)) courses in osteosarcoma, normal methotrexate clearance was successfully achieved in all courses administered with hydration >= 3,000 mL/m(2)/day compared with those administered with hydration <3,000 mL/m(2)/day (P=0.007). Furthermore, the courses administered with hydration <3,000 mL/m(2)/day and had delayed methotrexate clearance were more likely to develop adverse complications. Conclusion: Intravenous hydration of >= 3,000 mL/m(2)/day during HD-MTX administration is essentially required in osteosarcoma and can be considered as optional in ALL with HD-MTX <1.5g/m(2), especially in developing countries with limited monitoring of plasma methotrexate level.