High-dosed methotrexate in pediatric oncohematology: issues of toxicity of therapy

Methotrexate (МТХ) is one of the basic drugs that have significantly improved the survival rates of patients with hemoblastosis. For example, the results of treatment of patients with ALL and advanced stages of NHL with high-dosed (1-5 g/m2) methotrexate exceed 90%. Despite the high efficacy, treatment with methotrexate is associated with a range of toxic effects of the drug on organs and systems of the children's organism. The aim of the research was to conduct a comparative analysis of methotrexate toxicity effects in children using different hemoblastosis treatment protocols. This study is a systematic review. The most effective treatment programs used currently include protocols developed by the BFM group (Berlin-Frankfurt-Munster) and COALL (Germany), as well as a number of protocols of the American research groups CCSG, POG, StJCRH. As a result of the analysis, it was found that the protocols B-NHL BFM 90/95 and ALL-BFM-90 are characterized by high nephro- and hepatotoxicity of grade 3-4 (12.5% and 21.2% respectively), the protocol ALL-MB 91 is characterized by neurotoxicity of grade 3-4 (17.6%), protocols ALL-MB-2002; ALL-MB 2008 and ALL-MB 2015 are characterized by high hematological grade 3-4(64.3%) and skin toxicity grade 3-4 (14.5%). The ALL IC-BFM 2002 protocol can be considered sufficiently effective and safe. It has less severe skin toxicity (3.2%), hepatotoxicity (8.6%), nephrotoxicity (4.4%) of grades 3-4. The use of high-dose methotrexate in mM and MM protocols is not accompanied by a high incidence of severe toxic events with supportive therapy.