Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model

Anna M. Thomsen, Maria E. Gulinello, Jing Wen, Kjeld Schmiegelow, Peter D. Cole

Research output: Contribution to journalArticle

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Abstract

Liposomal cytarabine is currently being tested clinically as an alternative to intrathecal (IT) methotrexate (MTX) for preventing relapse within the central nervous system among patients with acute lymphoblastic leukemia. To compare the toxicity and cognitive deficits caused by IT MTX versus liposomal cytarabine, juvenile Long Evans rats were treated with IT injections of MTX 1 mg/kg×4 doses over 8 days, or liposomal cytarabine 0.8 mg once. Mean concentrations of free cytarabine in cerebrospinal fluid remained above the cytotoxic threshold of 0.4 μM for 2 weeks after dosing. Animals treated with liposomal cytarabine exhibited normal recognition and spatial memory 4 weeks after injection. In contrast, exposure to IT MTX led to impaired cognitive function. In addition, mean hematocrit on day 11 was significantly lower in the MTX-treated animals (30.8%; 95% confidence interval, 27.0%-34.7%; n=6) compared with that in the liposomal cytarabine-treated animals (39.5%; 95% confidence interval, 38.4%-40.6%; n=6; P<0.0001). Our data suggest that liposomal cytarabine induces fewer neurocognitive deficits and less acute hematologic toxicity compared with IT MTX. Liposomal cytarabine may therefore have therapeutic advantages over IT MTX, if it is equally effective in preventing relapse.

Original languageEnglish (US)
JournalJournal of Pediatric Hematology/Oncology
DOIs
StateAccepted/In press - Jun 26 2017

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Cytarabine
Methotrexate
Animal Models
Confidence Intervals
Recurrence
Spinal Injections
Long Evans Rats
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematocrit
Cognition
Cerebrospinal Fluid
Central Nervous System
Injections

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model. / Thomsen, Anna M.; Gulinello, Maria E.; Wen, Jing; Schmiegelow, Kjeld; Cole, Peter D.

In: Journal of Pediatric Hematology/Oncology, 26.06.2017.

Research output: Contribution to journalArticle

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