Rituximab-associated progressive multifocal leukoencephalopathy after a single cycle of R-CHOP for T-cell/histiocyte-rich large B-cell lymphoma

Abstract

Progressive multifocal leukoencephalopathy (PML) is a disease of immunocompromised patients caused by reactivation of the John Cunningham polyomavirus (JCV). A monoclonal anti-CD20 antibody rituximab is widely used as an important part of therapy for B-cell non-Hodgkin lymphomas and various autoimmune diseases. It is not fully explained how rituximab reactivates JCV.

In this report, we present the case of a 61-year-old man with T-cell/histiocyte-rich large B-cell lymphoma who was treated with R-CHOP and intrathecal methotrexate. Two weeks after the first R-CHOP course he developed dysarthria, diplopia, and disturbances in motor coordination. Based on CT/MRI results showing 3cm×2cm large hypodense white matter lesion in left cerebellar hemisphere, and detection of JCV in the cerebrospinal fluid (14300viral copies/mL), the patient was diagnosed with PML. Despite treatment attempt with cidofovir and IVIG, the patient's neurological status continued to worsen. He developed progressive motor neuron deficits but retained intact cognitive functions. The patient deceased nearly three months after onset of rituximab treatment.

Rituximab is a milestone in treatment of many hematological and autoimmune diseases. Considering how widespread has the use of rituximab become, the overall risk of developing PML is relatively low. Nevertheless, since the end of 1990s several reports were published on PML development in association with usage of rituximab. The authors would like to emphasize that although the total risk of PML occurrence in patients treated with rituximab is low, it is important that physicians administrating rituximab therapy are aware of this serious complication.