Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare central demyelinating neurological disease caused by John Cunningham virus (JCV) infection that has been described in the setting of severe dysfunction of cellular immunity such as the acquired immunodeficiency syndrome (AIDS). Biological targeted agents potentially inducing lymphocyte depletion and blockade of T-cell activation and trafficking have been progressively introduced for treatment of some chronic inflammatory and hematological malignancy. Cases of PML in patients under some of these treatments have been increasingly reported. We here review the underlying mechanisms, clinical characteristics, and preventive management of PML related with α4-integrin-targeted therapies (natalizumab, efalizumab) and other biological agents most clearly associated with an increased risk of PML (rituximab and alemtuzumab). Additionally, we discuss available information regarding newly introduced targeted therapies with post-marketing alarms with regard to PML risk as brentuximab and small molecules targeting intracellular signaling pathways.