Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.
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Linnebank et al. (2005) studied this question.
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