Successful Use of Intrathecal Carboxypeptidase G2 for Intrathecal Methotrexate Overdose: A Case Study and Review of the Literature

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Intrathecal (IT) methotrexate (MTX) overdose is a medical emergency. Available interventions include cerebrospinal fluid (CSF) drainage and ventriculolumbar perfusion, which are limited by timing and/or availability. Carboxypeptidase G2 hydrolyzes MTX into inactive metabolites and represents a promising agent for the treatment of IT MTX overdose. We set out to compile and review available animal data and human case reports using carboxypeptidase G2 by the IT route in the setting of IT MTX overdose. A review of the literature reveals promising results with IT carboxypeptidase G2, including a nearly 2-log reduction in CSF MTX levels and excellent neurologic outcomes in patients receiving 155 to 600 mg of IT MTX. Additionally, we have included a new report of a 66-year-old woman with primary CNS lymphoma who inadvertently received a 150-mg dose of IT MTX. Immediate treatment consisted of CSF drainage and intravenous dexamethasone and leucovorin. She subsequently received 2000 U of IT carboxypeptidase G2 11 hours after the overdose along with continued supportive care. CSF MTX levels promptly decreased and the patient was discharged with no residual neurologic deficits. IT carboxypeptidase G2 leads to rapid reduction of CSF MTX levels in patients with IT MTX overdose and is associated with excellent neurologic outcomes. Further studies are needed to clarify the role of this intervention in the context of existing drainage techniques.

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