The effect of the plasma methotrexate concentration during high-dose methotrexate therapy in childhood acute lymphoblastic leukemia

Abstract

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3–5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (C MTX) in ALL. The 24-h target peak C MTX (C 24h) was set at 33 μmol/l for low-risk (LR) and 65 μmol/l for intermediate/high-risk (IR/HR) groups. The median C 24h was 42.0 μmol/l and 69.7 μmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C 24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, C MTX does not exert an independent influence on the prognosis of childhood ALL.