Encephalopathy under systemic high-dose methotrexate therapy in acute lymphoblastic leukemia

Background: Methotrexate is a major component in the treatment of acute lym phoblastic leukemia in childhood as a preventive treatment of CNS and in or der to reduce testicular relapses. Unfortunately it can be severely neuroto xic. Case report: A 9 year old patient developed a methotrexate-encephalopathy a fter taking a high-dose of methotrexate for the first time within the treat ment regimen of ALL-therapy. The further treatment of the patient was carri ed on with a reduced dose of methotrexate and enlarged supportive therapy b eyond leucovorin rescue. Discussion: The development of methotrexate-encephalopathy is triggered by the disturbance of mainly folate metabolism and three other important metab olic pathways: adenosine, homocysteine, biopterine. It is possible to influ ence each of these pathways: In case of adenosine by use of theophylline as an antagonist; in both other pathways the addition of the essential cofact ors betaine and vitamine B6 (pathway of homocysteine) or tetrahydrobiopteri ne (pathway of biopterine) seems to be important.