The Neurotoxicity of High-dose Cytosine Arabinoside is Age-related

Fifteen patients with acute myeloid leukaemia were given a total of 17 courses of high-dose cytosine arabinoside (Ara-C). The median age of the patients was 37 years. Four patients developed severe irreversible neurotoxicity, three developed mild to moderate, reversible neurotoxicity, whereas eight patients had no toxicity. Of five patients over the age of 55 years given high dose Ara-C, four developed severe, irreversible neurotoxicity, but there were no severe episodes in nine patients aged 55 years or less. (P less than 0.01). At a dose of 3 g/m2 given intravenously every 12 hours for 3 days, three cases of severe irreversible neurotoxicity were noted in elderly patients. Neurotoxicity at this total dose has previously been considered unusual. Administration of high dose Ara-C at total doses of 18 g/m2 and over carries a risk of severe irreversible cerebellar toxicity that increases with age.