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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.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/m2 vs. 5 g/m2) 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.The overall morbidity of elimination delay was 12.1% in a total of 497 infusions. Patients with elimination delay had lower platelet count (P<0.01) and greater cumulative CF rescuing intensity (P<0.001). In 3-g group, children with elimination delay experienced severer oral mucous membrane damage (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 gastrointestinal (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).(1) HDMTX with 5 g/m2 is as safe as 3 g/m2 under adequate hydration and alkalization. Twenty-four–hour infusion is optimal. (2) Individualized dosing is necessary.