Effect of High Dose Methotrexate on Permeability Glycoprotein Serum Levels in Pediatric Patients with Acute Lymphocytic Leukemia

Abstract

Objectives To investigate the effect of high-dose methotrexate (HDMTX) on P-glycoprotein (P-gp) serum levels in pediatric patients with acute lymphocytic leukemia (ALL). Methods This controlled parallel clinical study was conducted between April 2020 and February 2022. Thirty-three pediatric patients with a confirmed diagnosis of ALL were included in this study (ALL group). Patients were enrolled before receiving the HDMTX protocol and after completion of the induction phase. Age, body mass index (BMI), and sex ratio matched healthy pediatric subjects were also included in this study and were selected from a primary care center (control group). Blood samples were collected from the healthy control group at baseline, and patients with ALL at baseline and after MTX therapy, for biochemical analysis of P-glycoprotein. MTX concentration was also determined in ALL samples after treatment to correlate with P-gp serum level. Results No statistically significant difference was observed in P-gp serum levels between the healthy pediatric subjects and patients with ALL before receiving MTX treatment. P-gp serum levels were significantly lower (P <0.05) in pediatric patients with ALL after MTX treatment in all age segments as compared to its levels before MTX treatment (baseline data). Moreover, there was no statistically significant difference in P-gp serum levels between the healthy pediatric subjects and pediatric patients with ALL after MTX treatment in the first age segments (4-7 years old). However, P-gp serum levels were significantly lower in pediatric patients with ALL who received MTX in both the 8-10 and the 11-14 years old segments compared to the healthy group. In addition, there was no significant correlation between MTX concentration and P-gp serum level in patients with ALL after MTX treatment. Conclusion High-dose methotrexate may exert a down-regulatory effect on P-gp serum level in pediatric patients with ALL. However, this needs further investigation. (ClinicalTrials.gov Identifier: NCT05021159, September 2021).