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
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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, Oct 04, 2015
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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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    ABSTRACT: Warm autoimmune hemolytic anemia (WAIHA) is one of four clinical types of autoimmune hemolytic anemia (AIHA), with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia-sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary) or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.
    Clinical and Developmental Immunology 09/2013; 2013:561852. DOI:10.1155/2013/561852 · 2.93 Impact Factor
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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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    ABSTRACT: The objective of this work was to study the efficacy and safety of pre-emptive rituximab (RTX) in a series of patients with severe relapsing granulomatosis with polyangiitis (GPA). GPA is a systemic vasculitis with a high relapse rate despite successful remission induction. Drug toxicity with repeated induction treatments and long-standing immunosuppression poses a problem. Based on the findings in reports on RTX for rheumatoid arthritis, we treated patients with severe relapsing GPA with pre-emptive RTX, 1,000 mg 2 weeks apart every 6 months, aiming at achieving sustainable remission. All patients at one centre with relapsing GPA in spite of traditional maintenance treatment, who had received more than or equal to three cycles of RTX as regularly repeated pre-emptive maintenance therapy every 6 months, were included in this retrospective study. Information on disease manifestations and activity, treatments, lab parameters and adverse events was extracted from the medical files. Of the 12 included patients, all with a positive proteinase 3-anti-neutrophil cytoplasmic antibodies, generalised disease and a median disease duration of 35 months (21-270), 92 % (11/12) achieved sustainable remission during a median follow-up time of 32 months (range 21-111) from first RTX treatment. Concomitant immunosuppressants were reduced. Infections were the most common adverse events, but infections were an issue also before the start of RTX. RTX administered every 6 months seems to be an effective maintenance treatment in a population with severe, relapsing long-standing GPA. Granulomatous as well as vasculitic manifestations responded equally well. Infections are a problem in this patient group but no new safety problems were identified.
    Clinical Rheumatology 08/2013; 33(6). DOI:10.1007/s10067-013-2351-y · 1.77 Impact Factor
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    • "There have been multiple reports of the development of PML as a side effect of the immunomodulatory therapies (monoclonal antibodies) natalizumab [15] [16] [17], rituximab [15] [18], efalizumab [15] [19], and infliximab [20] used to treat various chronic medical conditions. In addition, eight novel HPyVs have been discovered, at least one of which (MCV) does not appear to follow the traditional disease course described above for JCV and BKV [4]. "
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    ABSTRACT: JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host.
    Clinical and Developmental Immunology 05/2013; 2013(19):373579. DOI:10.1155/2013/373579 · 2.93 Impact Factor
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