Progressive multifocal leukoencephalopathy following rituximab therapy in HIV negative patients: A report of 57 cases from the Research on Adverse Drug Event and Reports (RADAR) project

Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO, USA.
Blood (Impact Factor: 10.45). 04/2009; 113(20):4834-40. DOI: 10.1182/blood-2008-10-186999
Source: PubMed


Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

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Available from: Daniele Focosi
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    • "About the side effects from the treatment, only one of the studies [23] showed 2 patients with severe infections and 1 patient with a myocardial infarction. The most severe potential long-term complication of rituximab treatment was reported by Carson et al. [28] with progressive multifocal leukoencephalopathy in 2 patients in 57 cases. Most recently, Barcellini et al. [29] completed a clinical trial to investigate the efficacy, safety, and response duration of lowdose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first-or secondline therapy in 23 patients with primary AIHA. "
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    • "Smoking did not emerge as a main predisposing risk factor for infections during RTX treatment in these patients. None of the patients developed late-onset neutropenia previously reported in patients with RA, SLE and vasculitis receiving RTX [27], neither have we experienced progressive multifocal leukoencephalopathy (only previously reported in patients with RA and SLE receiving RTX [28]). The infection rate after RTX was considerably higher in our patient group than that reported for RA patients (4.3/100 patient-years), treated with similar RTX treatment regimen [29]. "
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