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ORIGINAL ARTICLE
Year : 2013  |  Volume : 26  |  Issue : 2  |  Page : 138-144

Relationship between MTHFR polymorphism and side effects of high-dose methotrexate in pediatric acute lymphoblastic leukemia


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Correspondence Address:
Mahmoud A El-Hawy
Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin el Kom, 32511 Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.126146

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Objectives To study the relationship between plasma methotrexate (MTX) level, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and the occurrence of complications associated with high-dose methotrexate (HDMTX) in pediatric acute lymphoblastic leukemia (ALL). Background ALL is the most common type of cancer in children. Administration of HDMTX, followed by leucovorin rescue is an important component in the treatment of childhood ALL. MTX toxicity mainly includes mucositis, myelosuppression, and hepatic toxicity. MTX toxicity can vary with genetic variability in folate-metabolizing enzymes (e.g. MTHFR). Patients and methods A total of 26 ALL children were studied. Clinical assessments, laboratory detection of complete blood count parameters, detection of liver and renal functions before and after HDMTX, detection of MTX level after HDMTX, and PCR (restriction fragment length polymorphism) for the MTHFR polymorphism (C677T and A1298C) were carried out. Results The plasma MTX level was found to be related to HDMTX toxicity, especially mucositis. For the C677T MTHFR polymorphism, neutrophil recovery days were higher in TT, followed by CT and CC polymorphism, platelet recovery days were higher in TT, followed by CT and CC polymorphism, and days required for plasma MTX level to decrease to less than 0.1 μmol/l were higher in TT, followed by CT and CC polymorphism. For the A1298C polymorphism, postinfusion platelet count was lower in AA than in AC and CC polymorphism and platelet recovery days were lower in AA than in CC and AC polymorphism. Neutrophil recovery days and days required for plasma MTX level to decrease to less than 0.1 μmol/l were higher in AA, followed by AC and CC polymorphism. For the A1298C polymorphism, AC patients had a significantly higher overall survival than CC and AA patients. Conclusion The increase in plasma MTX level after HDMTX might be associated with an increase in the risk for complications. Genotyping of folate polymorphisms might be useful in ALL to optimize MTX therapy, reducing the associated toxicity with possible effects on survival.


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