Acute cerebellar toxicity induced by high dose of cytarabine (HiDAC): A case report

Abstract

Cytarabine is a pyrimidine analogue that is used for the treatment of acute myeloid leukemia at different doses. Standard doses of cytarabine are used for induction therapy, while high doses are used for post-remission (consolidation) and relapsed/refractory treatment. One of the major side effects of its high doses is acute cerebellar toxicity occurring in 10 to 25% of patients. We report a case that developed this side effect after receiving two doses of high-dose cytarabine. The patient’s symptoms improved after withholding the drug. Thereafter, the patient tolerated treatment continuation with lower doses.

Retreatment with full-dose cytarabine in a patient with previous neurological toxicity

“…Cerebellar toxicity is characterized by dysarthria, dysmetria, ataxia, diminished consciousness, dizziness, and eye disorders with nystagmus. 1,2 Although manifestations are usually mild, they can worsen and lead to encephalopathy, seizures, coma (more common in high-dose cytarabine regimens [≥2 g/m 2 ]), and kidney failure. 8,9…”

“…1 Cerebellar toxicity is characterized by dysarthria, dysmetria, ataxia, diminished consciousness, dizziness, and eye disorders with nystagmus. 1,2 Although manifestations are usually mild, they can worsen and lead to encephalopathy, seizures, coma (more common in high-dose cytarabine regimens [≥2 g/m 2 ]), and kidney failure. 8,9 Risk factors for cytarabine-induced cerebellar toxicity include age >50 years, cumulative high doses of cytarabine, dose dependency, kidney failure, recent or concomitant radiotherapy, a history of CNS disease, impaired liver function, and infusion of cytarabine over less than 1 h. Our patient had several risk factors: he was 66 years old, had mild kidney failure on the day of R-DHAP administration (creatinine 1.2 mg/dL; GFR 62.14 mL/min), received a high dose of cytarabine (13.36 g), and had a history of vertigo.…”

“…1 Although cytarabine-induced central nervous system (CNS) toxicity is well known and must be contemplated in high-dose regimens, little has been published on retreatment after a toxic event. [2][3][4][5] To our knowledge, only a few cases have been reported and all the patients needed a dose reduction. 2,6 The lack of information on cytarabine retreatment following CNS toxicity complicates decision-making, as the permanent withdrawal of a potentially curative drug in a patient with a hematological malignancy could have more risks than benefits.…”

“…[2][3][4][5] To our knowledge, only a few cases have been reported and all the patients needed a dose reduction. 2,6 The lack of information on cytarabine retreatment following CNS toxicity complicates decision-making, as the permanent withdrawal of a potentially curative drug in a patient with a hematological malignancy could have more risks than benefits. Patient consent has been obtained and approval for publication granted.…”

“…1 Although cytarabine-induced central nervous system (CNS) toxicity is well known and must be contemplated in high-dose regimens, little has been published on retreatment after a toxic event. 2 –5 To our knowledge, only a few cases have been reported and all the patients needed a dose reduction. 2,6…”