Neurotoxicity
Fludarabine
Fludarabine is a purine analog that inhibits DNA synthesis commonly used in hematologic malignancies or as part of a conditioning regimen prior to bone marrow transplant. Patients receiving fludarabine may experience delayed progressive encephalopathy that occurs several weeks to months after treatment. Most commonly the presenting symptoms include visual disturbances resulting from cortical blindness, visual pathway demyelination and retinal bipolar cell loss.
Neurotoxicity progresses to severe lethargy, confusion, coma and death. Toxicity is progressive, occurring over the course of weeks to months. The most strongly associated predictor of neurotoxicity is dose and cases occur with doses approaching 40 mg/m2. Diagnosis is difficult as the drug was likely discontinued weeks ago and is no longer presenting as an active medication. As such, other causes of encephalopathy such as opportunistic infection, seizure and progressive multifocal leukoencephalopathy should be ruled out. Lumbar puncture, EEG and MRI can help to differentiate other causes of encephalopathy.
MRI changes include white matter changes, hyperintense lesions in the peri-ventricular and peri atrial cerebral white matter on T2 and flair sequences. There is no treatment, and most patients suffer irreversible and severe neurologic dysfunction. Mortality is high in these patients.
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