Abstract
Introduction
Liposomal cytarabine (LC) is a sustained-release formulation of conventional cytarabine (CC) that remains within the cerebro-spinal fluid (CSF) about 40 times longer than CC when administered intrathecally. Its pharmacokinetic advantages and promising treatment data make LC an appealing option when treating central nervous system (CNS) involvement and administering prophylaxis against CNS relapse of aggressive lymphomas. While trials indicate LC is well-tolerated when separated from other CNS active agents or when given less frequently (Jabbour et al, Blood 2007),adverse effects (AE) are more common than with CC and can be serious despite the administration of prophylactic steroids (dexamethasone 4 mg twice daily for 5 days). These can include headache, nausea/vomiting, dizziness, fever, chemical aracnoiditis, seizures, cauda equina syndrome, and encephalitis. However, interpretation of tolerability is difficult due in part to variations in the type, dose, and route of administration of prophylactic steroids. Identification of the optimal dose and route of administration to mitigate these effects is warranted.
Methods
We reviewed our institutional database to evaluate the incidence of adverse effects when using concomitant intrathecal hydrocortisone to prevent LC adverse effects with or without systemic steroids. Data were collected for patients ≥18 years of age with complete clinical information available. The primary outcome was rate and type of AE at least probably due to LC in the opinion of the treating physician. Factors evaluated for contribution to this outcome were time from last LC, number of previous LC doses, total number of lumbar punctures in the previous 6 months, number of days of systemic steroids, and other CNS therapy at the time of LC.
Results
From September 2013 to June 2016 a total of 111 consecutive administrations of LC were evaluated among 53 patients. Twenty-six (49%) had CNS disease. Table 1 below summarizes patient details and incidence of toxicity per dose of LC. In 16 (14%) instances, no systemic steroids were given. Of those 16, 5 (31%) resulted in toxicities, 1 of which was altered mental status being defined as severe per common terminology criteria for adverse events (CTCAE) criteria. In 54 (49%) instances, patients received systemic steroids for 3 days or less. In 10 (19%) of these cases toxicity was observed, and was severe in 2 (20%) instances. Of the 57 (51%) doses that were given along with 4 days of systemic steroids or greater, 19 (33%) resulted in toxicity, 2 (11%) of which were considered severe. There were no documentations of seizures, neurologic sequelae, or death.
Conclusion
The overall rate of toxicity in this population parallels what has been reported with LC previously. A similar percentage of patients experienced toxicities and severe toxicities regardless of the concomitant administration of systemic steroids or the duration thereof. Intrathecal hydrocortisone may provide a viable alternative to the prescribed 5 days of prophylactic systemic steroids in patients with lymphoid malignancies receiving intrathecal therapy or prophylaxis with LC.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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