Abstract: Objective To explore the clinical safety of high-dose methotrexate (HD-MTX) by analyzing its adverse drug reactions (ADRs) in the treatment of childhood acute lymphoblastic leukemia (ALL), and discuss the Methods to prevent those ADRs. Methods Retrospective research was performed in 67 cases of ALL children diagnosed and treated in certain hospital. ADRs were recorded during the treatment. data analysis was conducted in patients concerning the blood concentration of MTX before and after the rescue of formyl tetrahydrofolate (CF). Results A total of 264 chemotherapy sessions with HD-MTX were performed in 67 children with ALL. Adverse reactions mainly included bone marrow suppression, gastrointestinal reactions, mucosal damage, liver toxicity, cardiotoxicity, renal toxicity, etc. No children experienced adverse events such as severe emesis or diarrhea, severe mucosal damage, severe cardiotoxicity, severe infection (level IV) or death (level V) during the treatment period. After HD-MTX treatment, statistic significance (P <0.05) for the incidence of emesis and mucosal damage were detected among patients grouped by different hazard level. But there was no such significant difference (P >0.05) for the incidence of blood plasma concentration of methotrexate> 1.0 μmol·L-1 after HD-MTX treatment for 44 hours or blood plasma concentration of methotrexate> 0.3 μmol·L-1 after HD-MTX treatment for 68 hours. Apart from the thrombocytopenia and myocardial enzyme elevation (P >0.05), there is statistic significance for the incidence of other 7 types of ADRs between delayed excretion group and normal excretion group (P <0.05). Conclusion The incidence of adverse reactions could be reduced within a certain range by the use of standardized HD-MTX treatment of children with ALL, CF rescue for MTX-intoxicated children in reference to MTX serum concentration, and effective measures to prevent and diminish adverse reactions, which could improve the life quality of those children.

Key words: high dose, methotrexate, children, acute lymphoblastic leukemia, adverse drug reaction