Involvement of the Variant but Not the or Variant in High-Dose Methotrexate-Induced Toxicity in Pediatric Acute Lymphoblastic Leukemia Patients in China.

PURPOSE

It remains unclear whether the and genetic variants are associated with methotrexate (MTX) elimination delay and high-dose MTX (HD-MTX) toxicities in the treatment of pediatric acute lymphoblastic leukemia (ALL). The aim of our study was to analyze the potential predictive role of and in toxicities and the relationship between these variants and MTX elimination delay during HD-MTX therapy in pediatric ALL patients.

PATIENTS AND METHODS

We conducted a retrospective study on ALL patients receiving HD-MTX treatment with available and genotype and 44-h plasma MTX levels. Logistic regression analyses and chi-square tests were used to assess the relationship between the variants and HD-MTX toxicities and MTX elimination delay.

RESULTS

Genotype frequencies were in Hardy-Weinberg equilibrium. MTX elimination delay did not significantly differ between and or . Leukopenia (P=0.028), neutropenia (P=0.034) and oral mucositis (P=0.023) were 6.444-fold, 4.978-fold and 9.643-fold increased, respectively, in homozygous genotype () patients compared to wild-type () patients. No significant association was found between the toxicities investigated and or .

CONCLUSION

This study showed that the homozygous allele genotype () is associated with increased MTX-related toxicities (leukopenia, neutropenia and oral mucositis). These results may help to distinguish pediatric ALL patients with a relatively high risk of MTX-related toxicities before HD-MTX infusion and optimize MTX treatment.