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J Pediatr Hematol Oncol. 2016 Oct;38(7):544-8. doi: 10.1097/MPH.0000000000000635.

Factors Affecting the Upper Limit of the Methotrexate (MTX) CSF Levels Achievable in Children With Brain Tumors Treated With High-dose Intravenous MTX.

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*Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel ‡Recanati Center for Medicine and Research and Clinical Pharmacology Unit, Rabin Medical Center-Beilinson Hospital, Petach Tikva †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.



Little has been published in the medical literature on serum and cerebrospinal fluid (CSF) methotrexate (MTX) levels in children with brain tumors.


Matched 24-hour serum and CSF MTX levels were studied after 113 treatments in 35 brain tumors patients.


A correlation between the 24-hour serum levels of MTX and MTX dosage was observed after 113 treatments in all 35 patients (r=0.39, P<0.001) but no statistical difference was found between CSF MTX levels in the irradiated and nonirradiated groups (P=0.12). Nonirradiated children received a lower dose of MTX (12.3±4.8 cf 14.8±3.7) (P=0.002). The 24-hour MTX CSF levels of these 2 groups were also found to be different (the nonirradiated group 7.6±9.8 cf 12.5±0.15.3). Using the Levene test for variances we found that these variances were not equal and therefore we used the Welch test which resulted in a P-value of 0.04. However, when an analysis of covariance was performed looking at evidence of CSF disease and MTX dose the radiation difference was no longer significant (P=0.15). The 24-hour CSF MTX levels in children without evidence of active CSF disease were consistently lower than those with active disease using a mixed-model analysis (P=0.002). Although a 24-hour CSF MTX level of at least 1 μM was observed after infusions of >5 g/m MTX in previously irradiated children and after infusion of ≥10 g/m in nonirradiated children this difference did not reach statistical significance. CSF MTX levels plateau at doses of MTX 15 g/m putting in doubt the value of administering even higher doses of MTX.


The 24-hour MTX CSF levels are higher in patients with active CSF disease. Doses of <10 gm/m in children with brain tumors may not achieve a guaranteed 24-hour MTX CSF level of 1 μM. There may be little value in a given dose of >15 g/m MTX as CSF levels plateau at this dose.

[Indexed for MEDLINE]

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