Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinatin g disorder of the central nervous system usually affecting immunocompromise d individuals and is due to infection of the oligodendrocytes by the JC vir us. A case of PML in a chronic lymphocytic leukemia (CLL) patient treated w ith fludarabine is reported, representing the second such instance in which the diagnosis of the neurological disorder was established by brain biopsy . A 61-year-old man with a 14-year history of B-cell type CLL, for which he had received chlorambucil therapy 10 years earlier, developed progressive paresis of both left extremities at 7 months of receiving low doses of oral fludarabine, when his CD4 count has decreased to 0.08x10(9)/1. Cranial mag netic resonance imaging revealed a subcortical focal lesion at the right pr ecentral gyrus and a focal lesion at the right thalamus, and a stereotactic brain biopsy showed pathological findings consistent with PML, namely seve re myelin breakdown, reactive astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing granular basophilic inclusions, whereas t he presence of the JC virus was demonstrated by in situ hybridization. The present case, in addition to a few previously reported, calls attention to the possibility that severe neurological side effects can be associated wit h the immunosuppression provoked by the use of fludarabine in CLL patients.