High dose methotrexate in acute lymphocytic leukemia in childhood

Gonadal and other types of leukemic "sanctuaries" are probably the main causes of hematological relapse in the treatment of acute leukemia. The introduction of high-dose Methotrexate (HDM) in a consolidation phase is based on theoretical considerations and the use of HDM in malignant tumors. Three courses of Methotrexate, 500 mg/sq.m. at 3-weekly intervals, has been used as part of a consolidation therapy in Norway during the last two years to 59 children with ALL and one with AML. One child died following HDM. Postmortem examination showed that she was not in complete remission at the time. Among 154 courses of HDM in the 60 patients were eight severe reactions, including six cases of allergic-toxic skin reactions. Two patients developed a Stevens-Johnson's like syndrome. Stomatitis was common in those with toxic reactions. The risk of HDM in patients who are not in complete remission is stressed and the use of rescue therapy with two doses of Leukovorin instead of one is recommended. Forty of forty-two children in 1st complete remission have been in sustained primary remission for 4 to 28 months. Two of these 40 children died after about a year from infections. Only two patients so far have relapsed.