Association of Methylenetetrahydrofolate Reductase Gene Polymorphism with Blood Methotrexate Concentration and Adverse Reactions in Children with Acute Lymphoblastic Leukemia
OBJECTIVE To investigate the correlation between polymorphisms of MTHFR(1298A＞C)and MTHFR(677C＞T)and the blood concentration and adverse reactions of methotrexate(MTX).METHODS A total of 185 children with acutelymphoblastic leukemia(ALL)admitted to Shanghai Children's Hospital from October 2014 to December 2021 were selected to collect laboratory test indicators such as MTHFR(1298A＞C)and MTHFR(677C＞T)genotype,adverse reactions,and blood concentration.RESULTS The overall incidence of adverse reactions after using MTX in 185 children was 95.1％.The incidence of adverse reactions between the two genotypes of MTHFR(A1298C)was not statistically significant,except for the difference in neutropenia(P=0.006);the incidence of adverse reactions in ALL children with three genotypes of MTHFR(C677T)was not statistically significant except for neutropenia(P=0.041/0.012),gastrointestinal reactions(P=0.037/0.011),and mucosal toxicity(P=0.039/0.016);there was a statistically significant difference in MTX plasma concentration among ALL patients with three genotypes of MTHFR(C677T)at 24 h(P=0.021);there was a statistically significant difference in the incidence of calcium folinate doubling rescue among ALL patients with three genotypes of MTHFR(677C＞T)(P=0.007/0.002).CONCLUSION Polymorphisms in MTHFR(1298A＞C)and MTHFR(677C＞T)may not be good indicators for predicting MTX chemotherapy in children with ALL.The importance of doubling rescue is emphasized,as doubling rescue can significantly reduce the incidence of such adverse reactions in children with high incidence of mucosal toxicity and bone marrow toxicity.
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