Feasibility and toxicity of intrathecal liposomal cytarabine in 5 children and young adults with refractory neoplastic meningitis.
Intrathecal (IT) treatment of neoplastic meningitis secondary to relapsed or refractory malignancies is a major challenge for clinicians. We studied feasibility and toxicity of IT administered liposomal cytarabine on a compassionate basis in 5 patients (male, n=4; female, n=1; age at diagnosis 5 to 18 y) with recurrent acute lymphoblastic leukemia (n=3), primary refractory acute myeloid leukemia (n=1), or relapsed medulloblastoma (n=1). All of them had evidence of meningeal involvement as shown by presence of leukemic blasts or solid tumor cells on cytologic examination of cerebrospinal fluid and were refractory to standard central nervous system (CNS) therapy. A total of 33 doses were given. Leukemic blasts or solid tumor cells were cleared from cerebrospinal fluid in all patients. IT liposomal cytarabine was well tolerated in 2 patients, but may have contributed to neurologic side effects in 2 other patients with 1 patient who received high-dose methotrexate 96 hours before IT liposomal cytarabine developing transient encephalopathy. Another patient experienced seizures after 6 well-tolerated doses of IT liposomal cytarabine. In the fifth patient, treatment with IT liposomal cytarabine was not continued after a single dose because of toxic cauda equina syndrome, resulting from previous intensive CNS therapy. If administered simultaneously to other neurotoxic drugs, IT liposomal cytarabine may contribute to neurologic side effects in patients who had received prior intensive CNS-directed therapy. IT liposomal cytarabine should, therefore, be used cautiously, if a patient receives other potentially neurotoxic drugs simultaneously.
Benesch
Martin
M
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. martin.benesch@klinikum-graz.at
Sovinz
Petra
P
Krammer
Barbara
B
Lackner
Herwig
H
Mann
Georg
G
Schwinger
Wolfgang
W
Gadner
Helmut
H
Urban
Christian
C
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid / Q000556:secondary* / Q000628:therapy*; D008581:Meningitis / Q000628:therapy
D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D003561:Cytarabine