Central nervous system toxicity of high-dose cytosine arabinoside

Ten patients with refractory acute leukemia were treated with high-dose cytosine arabinoside (Ara-C) infusions. Nine patients had previously achieved at least one complete remission using standard chemotherapy protocols that include cytosine arabinoside. Eight of the ten had been on maintenance therapy. Twelve courses of treatment were given, with the cytosine arabinoside infused over 1-2 hours in a dose of 3 gm/m2. Each course consisted of 12 to 16 doses given at 12-hour intervals. The drug was generally well tolerated but five patients developed central nervous system symptoms characterized by ataxia, dysphasia, nystagmus, dysdiadochokinesis, and a decreased level of consciousness. These changes began 3 to 34 days after the initiation of therapy and were severe at the time of death in two of the patients. One complete and one partial remission, lasting 2.5 months and 1 month, respectively, were documented. This experience suggests that high-dose Ara-C is of limited usefulness in refractory acute leukemia and may be frequently associated with significant neurotoxicity.