Evaluation of Relationship of the Methylene Tetrahydrofolate Reductase Enzyme Polymorphisms with Serum Methotrexate Concentration and Toxicity in Acute Lymphoblastic Leukemia Patients Treated with High Dose Methotrexate Infusion.

摘要

Background: Methotrexate (MTX) blocks Methylene Tetrahydrofolate Reductase (MTHFR) Enzyme thereby, interrupt folate metabolism, it is used in the treatment of cancer and autoimmune disorders. Aim and Objectives: The present study aimed to evaluate the relationship of the MTHFR polymorphisms with serum MTX concentration and its toxicity in Acute Lymphoblastic Leukemia (ALL) patients treated with high dose MTX infusion. Material and Methods: Level of Serum MTX was measured, along with the detection of MTHFR polymorphisms viz. C677T and A1298C by Polymerase Chain Reaction (PCR) followed by DNA sequencing. The percentages of toxicity developed in patients were calculated among the wild type and carriers for both polymorphisms and were compared between the groups. Results:The majority of patients 36 (72 %) were wild type for the C677T polymorphism and 32 (64 %) of patients were carriers for the A1298C polymorphism [48% heterozygous (AC), and 16 % homozygous (CC)]. Among 50 ALL patients studied, significant difference was noted in the genotype and allele frequencies for C677T polymorphism, while only allele frequencies differed significantly for A1298C polymorphism. The serum MTX level at 48 hours after the start of High Dose MTX (HDMTX) infusion of the C677T variant (CT) was slightly high in all four cycles however, in the first cycle, there was a significant increase in the level of MTX. There was no significant difference in the serum MTX level found in all four cycles between patients wild type and carriers for A1298C polymorphism. For A1298C polymorphism, the mean SGPT level in carriers was significantly high as compared to wild type. Conclusion: The present study concludes that patients with C667T variant had elevated serum MTX concentration at 48 hours after the start of HDMTX infusion.