Abstract:

Objective To investigate the correlation of genetic polymorphism of RFC1G80A and the therapeutic reaction of high dose methotrexate (HDMTX) for treating the childhood acute lymphoblastic leukemia (ALL). Methods Sixty-eight patients (280 case-times) treated by HDMTX (dose>1 g/m²) were selected. The genetic polymorphism of RFC1 G80A was detected before MTX treatment. Plasma MTX level, liver and kidney function, and peripheral blood cell count were detected regularly. Toxic side effects of MTX and prognosis were observed and their correlation was evaluated. Results The genetic polymorphism of RFC1 G80A was correlated with toxic side effects of MTX. The risks of moderate and severe hepatotoxicity and myelosuppression of RFC1-AA genotype were 7.28 and 2.8 times higher than those of RFC1-GG genotype (P=0.000, 0.005), therefore RFC1-AA genotype was a risk indicator for predicting toxic side effects of HDMTX. The differences of elimination delay of MTX and prognosis of genotypes of RFC1 G80A were not statistically significant (P>0.05). Conclusion The genetic polymorphism of RFC1G80A is correlated with moderate and severe hepatotoxicity and myelosuppression after HDMTX treatment and can be used as a risk indicator for predicting toxic side effects of HDMTX.

Key words: methotrexate, reduced folate carrier, drug concentration, toxic side effects, acute lymphoblastic leukemia, children