Progressive multifocal leukoencephalopathy after fludarabine therapy for low-grade lymphoproliferative disease

Fludarabine is becoming the initial therapy for low-grade lymphoproliferative malignancies, such as CLL and follicular lymphoma. Fludarabine is highly immunosuppressive in addition to being myelosuppressive and has been associated with neurotoxicity. Progressive multifocal leukoencephalopathy (PML) is an infection with JC virus of the white matter of the central nervous system seen mostly in immunosuppressed patients. We describe two patients treated with fludarabine who developed PML. Immunolabeling was positive for JCV in both patients, but PCR was repeatedly negative in one of them. We suggest that fludarabine may increase the risk of PML in patients with lymphoproliferative diseases. (C) 2002 Wiley-Liss, Inc.