Prospective Evaluation of Single-Time-Point Methotrexate Monitoring During High-Dose Therapy in Pediatric Leukemias...

Conventional multi-time point monitoring during high-dose methotrexate (HD-MTX) therapy is often impractical in low- and middle-income countries (LMICs). A simplified single-time-point monitoring strategy may offer a feasible alternative.

To determine the proportion of patients achieving adequate MTX clearance (≤0.4 µmol/L) at 48 h following initiation of HD-MTX.

In this prospective observational study, children with high-risk B-lineage and T-cell acute lymphoblastic leukemia receiving HD-MTX were enrolled. Single time point MTX levels were measured 48 h from initiation of infusion. MTX level >0.4 µmol/L received intensified hydration and leucovorin rescue. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Patients with pre-existing renal insufficiency or prior Grades 3 and 4 MTX toxicity were excluded.

Thirty-two children (age 2-12 years) undergoing 106 cycles of HD-MTX were evaluated. MTX clearance at 48 h was achieved in 74.5% (79/106). Delayed clearance normalized at 72 h in 5/16 retested cycles. Age >7 years (p = 0.025) and higher baseline serum creatinine (p = 0.022) predicted delayed clearance. Elevated 48-h levels correlated with neutropenia (13%, p = 0.0096), transaminitis, mucositis, and acute kidney injury occurred in 10.4%, 7.5%, and 3.8% of cycles.

A single 48-h MTX level can facilitate discharge decisions in approximately 75% of treatment cycles in a preselected cohort of patients. This approach may provide a pragmatic and cost-effective strategy in resource-limited settings, though its safety in unselected populations remains to be established. Validation in larger, unselected cohorts is needed before broad implementation can be recommended.