Neurologic complications after intrathecal liposomal cytarabine in combination with systemic polychemotherapy in primary CNS lymphoma

Abstract

Intrathecal application of liposomal cytarabine (Ara-C) (DepoCyte(®)) has been associated with neurotoxicity when applied as part of a polychemotherapy regimen. Patients with primary central nervous system lymphoma treated with high-dose systemic methotrexate (MTX)- and Ara-C-based polychemotherapy including six cycles of liposomal Ara-C (50 mg intrathecally every 3 weeks) were prospectively monitored for neurotoxic side-effects. Between November 2005 and February 2009, 149 intrathecal applications of liposomal cytarabine (DepoCyte(®)) were carried out in 33 patients, 7 (21%) of whom developed an incomplete conus medullaris/cauda equina syndrome with incontinence for bladder (6) and bowel function (3) or lumbosacral polyradicular paresis (1), resolving only incompletely over a follow-up period of 9-30 months. In six of these seven patients, lumbosacral magnetic resonance imaging (MRI) was negative for leptomeningeal infiltration or arachnoiditis. Cerebrospinal fluid (CSF) analysis performed in six of these seven patients showed normal cell count in all and increased total protein in four of them. One patient among these seven suffered a seizure without other identifiable causes. Conus/cauda syndrome has to be considered as a serious potential neurotoxic side-effect in patients receiving liposomal Ara-C as part of a multimodal regimen including high-dose systemic MTX and Ara-C.