Cytarabine

Respiratory

Two cases of respiratory failure occurred during induction chemotherapy for acute myelomonocytic leukemia with cytarabine and all-trans-retinoic acid [ ]. The authors attributed this to a manifestation of the retinoic acid syndrome. Both patients developed acute respiratory failure with widespread pulmonary infiltrates about 60 hours after starting chemotherapy. Both were managed successfully using high-dose dexamethasone and ventilation.

Nervous system

Central nervous system disturbances, especially impaired cerebellar function, limit doses of cytarabine, and age is an important predictive factor. Of 418 patients who received 36–48 g/m ² only 35 (8%) had severe cerebellar toxicity, which was irreversible or fatal in 4 (1%) [ ]. Patients over 50 years of age were significantly more likely to develop cerebellar problems than younger patients (26/137, 19%, compared with 9/281, 3%); a second course did not increase the incidence, implying that it is the individual rather than the cumulative dose that is important.

The cerebellar syndrome is the most common complication of high-dose cytarabine therapy. In a study of the cerebellar syndrome caused by cytarabine [ ], in which it was found in seven of 30 patients treated, symptoms of toxicity appeared between the third and seventh days of chemotherapy, manifesting first as lethargy and confusion [ ]. Within the next 24 hours there were signs of cerebellar dysfunction, including dysarthria, ataxia, tremor, nystagmus, and dysmetria. In most patients in whom neurotoxicity developed, liver function worsened during chemotherapy. Abnormal liver function at the start of therapy and the development of neurotoxicity appear to be linked. The symptoms of neurotoxicity resolved within 4–49 days.

Aseptic meningitis can also occur in patients given cytarabine [ , ], and signs of cerebellar dysfunction after the administration of cytarabine 24 g/m ² have been reported in association with aseptic meningitis [ ].