Methotrexate elimination and toxicity: MTHFR 677C>T polymorphism in patients with primary CNS lymphoma treated with high-dose methotrexate

Yun Jung Choi, Hyangmin Park, Ji Sung Lee, Ju Yeon Lee, Shin Kim, Tae Won Kim, Jung Sun Park, Jeong Eun Kim, Dok Hyun Yoon, Cheolwon Suh

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 MTX 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.

Original languageEnglish (US)
Pages (from-to)504-509
Number of pages6
JournalHematological Oncology
Volume35
Issue number4
DOIs
StatePublished - Dec 2017

Bibliographical note

Publisher Copyright:
Copyright © 2016 John Wiley & Sons, Ltd.

Keywords

  • MTHFR 677C>T polymorphism
  • high-dose methotrexate
  • toxicity

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