Folate Status and Methotrexate-Induced Toxicities in Pediatric Acute Lymphoblastic Leukemia

Background: Methotrexate-induced toxicities often occur in pediatric ALL undergoing chemotherapy. Methotrexate is inhibiting folate metabolism so no DNA synthesis occurs. Folate deficiency can occur before and after administration of methotrexate high dose (MTX-HD). This also may affect the outcome of chemotherapy. However, there has been limited research on folate levels in blood during MTX-HD therapy and its correlation to toxicity.Objective: To analyze the correlation between folate levels and toxicity following high-dose methotrexate (MTX-HD) administration in pediatric patients with acute lymphoblastic leukemia (ALL).Methods: This prospective observational study included ۳۱ pediatric ALL patients aged ۱-۱۸ years undergoing consolidation phase chemotherapy. Serum folate levels were measured before and after MTX-HD using CalSet Folate, and MTX-induced toxicities were observed within ۴۸ hours post-administration. Data were analyzed using the Wilcoxon Signed Rank test and Spearman Correlation Test, with p<۰.۰۵ considered significant.Results: Thirty-one subjects were included, with a median age of ۴ years. Median folate levels increased significantly from ۲۳.۵ ng/mL before to ۴۰ ng/mL after MTX-HD (p<۰.۰۵). Common toxicities included mucositis (۱۰۰%), neutropenia (۴۵.۲%), DILI (۳۵.۵%), and AKI (۶.۴%). No significant correlation was found between folate levels and these toxicities (p>۰.۰۵).Conclusion: Significant differences in folate levels were observed before and after MTX-HD. Despite high folate levels, MTX-induced toxicities still occurred, suggesting other factors may contribute to toxicity.

کلیدواژه ها:

pediatric acute lymphoblastic leukemia ، methotrexate ، Folate ، Toxicity