Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma

Noriko Shimasaki, Tetsuya Mori, Hazuki Samejima, Reiko Sato, Hiroyuki Shimada, Naohisa Yahagi, Chiharu Torii, Hiroki Yoshihara, Yusuke Tanigawara, Takao Takahashi, Kenjiro Kosaki

研究成果: Article査読

86 被引用数 (Scopus)

抄録

The authors investigated whether high-dose methotrexate-induced toxicity differed according to the presence of methylenetetrahydrofolate reductase (MTHFR) or reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15 children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were treated using protocols that included high-dose methotrexate (3.0 g/m2), for an overall total of 43 courses. Methotrexate-induced toxicities and the plasma methotrexate concentrations were evaluated retrospectively. Hematologic toxicity was the most frequently observed toxicity, appearing in 87% of the patients. In a subset of patients (47%), elevation of liver transaminase levels showed a repeated tendency to develop. High plasma methotrexate concentrations at 48 hours after the methotrexate infusion were not significantly related to methotrexate-induced toxicities except for mucositis. A generalized estimating equation analysis revealed that vomiting during the high-dose methotrexate treatment was more pronounced in patients who had a larger number of G alleles at the RFC1 80G>A polymorphism. No significant differences in the development of other toxicities or in the plasma methotrexate concentrations were observed for the different MTHFR 677C>T or RFC1 80G>A polymorphisms. This study suggests but does not prove that the RFC1 80G>A polymorphism may contribute to interindividual variability in responses to high-dose methotrexate.

本文言語English
ページ(範囲)64-68
ページ数5
ジャーナルJournal of Pediatric Hematology/Oncology
28
2
DOI
出版ステータスPublished - 2006 2月 1

ASJC Scopus subject areas

  • 小児科学、周産期医学および子どもの健康
  • 血液学
  • 腫瘍学

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