Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment
Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment
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DOI：
10.1182/blood-2002-06-1636
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发表时间：
2003-01-15
期刊：
影响因子：
20.3
通讯作者：
Shuman, MA
中科院分区：
文献类型：
--
作者：
Rubenstein, JL;Combs, D;Shuman, MA
Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSIF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSIF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in Patients with recurrent lymphomatous meningitis will be implemented based on these findings. (C) 2003 by The American Society of Hematology.
