Relationship Between Plasma Methotrexate Level At 42 Hours And Toxicity After High-Dose Methotrexate In Children With Acute Lymphoblastic Leukemia: A Prospective Cohort Study

Abstract

Background : Despite its efficacy in treating acute lymphoblastic leukemia, high-dose methotrexate (HDMTX) can cause serious side effects. Methotrexate monitoring (MTX) is challenging in resource-limited settings.
Objective: The aim of this study was to compare the toxicities of different doses of HDMTX and investigate the relationship between plasma MTX levels at 42 hours from the start of HDMTX infusion (MTX42) and possible toxicities.
Patients and Methods: This prospective study consecutively enrolled 30 children with acute lymphoblastic leukemia in Egypt between May 2018 and July 2020. Patients were stratified into two risk groups according to the TOTAL therapy study XV protocol. MTX was administered intravenously as a 24-hr infusion (low-risk: 2.5 g/m2, standard/high-risk: 5 g/m2). The Common Terminology Criteria for Adverse Events v.4.03 was used to report toxicity. MTX42 levels were estimated after the first HDMTX infusion.
Results: The most common toxicities were anemia and neutropenia in both groups. There was no statistically significant difference between the two groups regarding toxicities. Moreover, there was no significant difference between patients with and without different toxicities regarding MTX42 levels.
Conclusion: Higher MTX doses can be safely administered while applying proper supportive measures. Although plasma MTX level monitoring is recommended, MTX42 levels failed to predict different toxicities.