Progressive multifocal leukoencephalopathy in chronic lymphocytic leukemia after treatment with fludarabine

A 65-year-old man with chronic lymphocytic leukemia (CLL) diagnosed 11 years ago and treated with standard dose of fludarabine developed a rapidly fatal progressive neurological syndrome. Differential diagnoses included brain infiltration by CLL as opposed to progressive multifocal leukoencephalopathy (PML). A magnetic resonance imaging (MRI) scan showed a hyperintense T2-weighted signal in the left frontal region. Cerebro-spinal fluid polymerase chain reaction (PCR) was positive for virus JC (JCV). These findings were compatible with the diagnosis of PML. Fludarabine has been used to treat acute leukemias, CLL and follicular lymphomas. Its toxicity includes myelosuppression, immunosuppression and sporadic life-threatening neurotoxicity, although standard doses of it are considered safe. Late-onset fatal cerebral dysfunction caused by JCV after standard-dose fludarabine has been described previously. The widespread and increasing use of fludarabine makes it interesting to define the potential of standard doses of fludarabine for causing severe neurological side-effects such as PML.