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The effect of the plasma methotrexate concentration during high-dose methotrexate therapy in childhood acute
Chan Liao1, Jing Nie2,3, Xiao-Jun Xu1
1Department of Pediatric Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, China.
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 (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 μmol/l for low-risk (LR) and 65 μmol/l for intermediate/high-risk (IR/HR) groups. The median C24h 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 C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.
