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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3214-3218.
Prepublished online as a Blood First Edition Paper on January 5, 2007; DOI 10.1182/blood-2006-08-043646.
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Submitted August 29, 2006
Accepted November 27, 2006
Neurological complications associated with intrathecal
liposomal cytarabine given prophylactically in
combination with high dose methotrexate and cytarabine
to patients with acute lymphocytic leukemia
Elias Jabbour, Susan O'Brien, Hagop Kantarjian, Guillermo Garcia-Manero, Alessandra Ferrajoli, Farhad Ravandi, Maria Cabanillas, and Deborah A Thomas*
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX
* Corresponding author; email: debthomas{at}mdanderson.org.
Central nervous system (CNS) prophylaxis has led to a significant improvement in the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal cytarabine (DepocytTM, Enzon Pharmaceuticals, Pisataway, NJ and Skye Pharma Inc., San Diego, CA), an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has been shown to be safe and effective in the treatment of neoplastic meningitis. Liposomal cytarabine was given for CNS prophylaxis to 31 patients with newly diagnosed ALL. All patients were treated concurrently with hyper-CVAD chemotherapy including high dose methotrexate (MTX) and cytarabine on alternating courses. Liposomal cytarabine 50 mg was given on days 2 and 15 of hyper-CVAD and day 10 of high dose MTX and cytarabine courses until completion of either 3, 6 or 10 IT treatments depending on risk for CNS disease. Five patients (16%) experienced serious unexpected neurotoxicity, including seizures, papilledema, cauda equina syndrome (n=2) and encephalitis after a median of 4 IT administrations of liposomal cytarabine. Toxicities usually manifested after the MTX and cytarabine courses. One patient died with progressive encephalitis. After a median follow-up of 7 months, no isolated CNS relapses have been observed. Liposomal cytarabine given via intrathecal route concomitantly with systemic chemotherapy that crosses the blood-brain barrier such as high dose MTX and cytarabine can result in significant neurotoxicity.
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