[Influence of Methylenetetrahydrofolate Reductase Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell Lymphoma Patients]

Objective: To investigate the effect of genetic polymorphism of (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients.

Methods: Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included, and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed.

Results: Among the 58 pediatric patients, the number of CC, CT, and TT genotypes for was 33, 19 and 6, respectively. A total of 101 courses of HD-MTX therapy were counted, of which plasma MTX level >0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses, ≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level >0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis ( <0.05). Compared with wild-type (CC genotype), patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression, manifested as anemia, leucopenia, neutropenia and thrombocytopenia. However, plasma MTX level at 48 h was not associated with gene polymorphism.

Conclusion: The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of gene is not related to plasma MTX concentration in children with mature B-cell lymphoma, but is related to grade III to IV hematological toxicity.