Journal
HEMATOLOGICAL ONCOLOGY
Volume 35, Issue 4, Pages 504-509Publisher
WILEY
DOI: 10.1002/hon.2363
Keywords
high-dose methotrexate; MTHFR 677C > T polymorphism; toxicity
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Funding
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI14C1731]
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The genetic association of the methylenetetrahydrofolate reductase gene (MTHFR)677C>T polymorphism with methotrexate (MTX)-associated toxicity has been evaluated and conflicting results have been reported. The substantial heterogeneity of the studied population was suggested to be a possible explanation because ethnicity, MTX dose, coadministered chemotherapeutic agents, and folinate rescue dosage regimen could alter the MTX toxicity profile. The patient population was homogenized by limiting the cancer type to primary central nervous system lymphoma and chemotherapy protocol to a high-dose MIX monotherapy regimen. A total of 111 patients with 402 chemotherapy courses were analyzed. MTHFR 677C>T polymorphism was identified as an independent predictive marker for MTX-associated hematologic toxicity (odds ratio. 2.60; 95% confidence interval, 1.32-5.09; P = .0055). Clinically significant nephrotoxicity occurred in patients without delayed elimination, suggesting roles for factors other than serum MTX levels. MTX-induced hepatotoxicity and oral mucositis occurred independently of plasma MTX levels.
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