Retrospective study on elimination delay of methotrexate in high-dose therapy of childhood acute lymphoblastic leukemia in China

Objectives: The aim of this study was to observe the morbidity of elimination delay in Chinese children with acute lymphoblastic leukemia during high-dose methotrexate (HDMTX) therapy and the toxicities. Patients and Methods: A total of 121 children with acute lymphoblastic leukemia on HDMTX therapy were enrolled into this study. Patients were divided into groups on the basis of either dosage (3 g/m(2) vs. 5 g/m(2)) or infusion duration (7 h vs. 24 h). CF/MTX index was used to determine the calcium folinate (CF) rescuing intensity and toxicity was evaluated according to World Health Organization criteria. Results: The overall morbidity of elimination delay was 12.1% in a total of 497 infusions. Patients with elimination delay had lower platelet count (P < 0.0 1) and greater cumulative CF rescuing intensity (P < 0.001). In 3-g group, children with elimination delay experienced severer oral mucous membrane damage 9 (P < 0.05) than those without elimination delay, and postponement of following chemotherapy (P = 0.001). No significant difference was found in morbidity of elimination delay between 3 and 5-g groups (P > 0.05) or 7 and 24-hour infusion groups (P > 0.05). The only raised adverse effect in 5-g group was aastrointestinal (P = 0.003) as compared with 3-g group. The CF rescuing intensity of 5-g group without elimination delay was lower than that of the 3-g group (P < 0.01). Conclusions: (1) HDMTX with 5 g/m(2) is as safe as 3 g/m(2) under adequate hydration and alkalization. Twenty-four hour infusion is optimal. (2) Individualized dosing is necessary.