Objective: Methotrexate (MTX) is an anticancer and anti-inflammatory drug widely used to treat various diseases. Some patients are more susceptible to toxicity, some show resistance to chemotherapy. The most conducted studies have investigated the effect of gene polymorphism on MTX toxicity, and little data are available about the relationship between MTX dose and type of toxicity.

Materials and Methods: In the present meta-analysis, we evaluated 20 studies that focused on the association between MTX dose and MTX-related toxicities.

Results: Our pooled analysis showed Gl toxicity has higher prevalence (p= 0.51, 95% CI (0.10, 0.91)) compared to other toxicities, follow by hematologic toxicity (p = 0.41, 95% CI (0.25, 0.56)) and mucositis (p = 0.41, 95% CI (0.17, 0.65)). Whereas, renal toxicity (p = 0.32 [95% CI (0.12, 0.52)) showed the lowest prevalence. The results showed a significant prevalence of all toxicity (except the hematologic toxicity) in different dosages. Also, the dose of 12 mg showed higher toxicity than other dosages.

Conclusions: To reduce MTX-related adverse events in pediatrics, our findings suggested that more investigations for replacement of MTX are required.