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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4834-4840. Prepublished online as a Blood First Edition Paper on March 5, 2009; DOI 10.1182/blood-2008-10-186999. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-10-186999v1 113/20/4834    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Carson, K. R. Articles by Bennett, C. L. Search for Related Content PubMed PubMed Citation Articles by Carson, K. R. Articles by Bennett, C. L. Related Collections Free Research Articles Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project Kenneth R. Carson1, Andrew M. Evens2,3, Elizabeth A. Richey2, Thomas M. Habermann4, Daniele Focosi5, John F. Seymour6, Jacob Laubach7, Susie D. Bawn8, Leo I. Gordon2,3, Jane N. Winter2,3, Richard R. Furman9, Julie M. Vose10, Andrew D. Zelenetz9,11, Ronac Mamtani9, Dennis W. Raisch12, Gary W. Dorshimer13, Steven T. Rosen2,3, Kenji Muro14, Numa R. Gottardi-Littell15, Robert L. Talley16, Oliver Sartor17, David Green2,3, Eugene O. Major18, and Charles L. Bennett2,3,19 1 Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO; 2 Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 3 Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; 4 Department of Hematology, Mayo Clinic College of Medicine, Rochester, MN; 5 Division of Hematology, University of Pisa, Pisa, Italy; 6 Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, East Melbourne, Australia; 7 Dana-Farber Cancer Institute, Boston, MA; 8 Division of Hematology/Oncology, Stanford University School of Medicine, CA; 9 Division of Hematology/Oncology, New York Presbyterian Hospital-Cornell Medical Center, NY; 10 Section of Hematology/Oncology, University of Nebraska Medical Center, Omaha; 11 Division of Hematology/Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY; 12 Veterans Administration Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, University of New Mexico, Albuquerque; 13 Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia; Departments of14 Neurological Surgery and 15 Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 16 Kansas City Cancer Center, MO; 17 Tulane Medical School, New Orleans, LA; 18 Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; and 19 Veterans Administration Center for the Management of Complex Chronic Conditions, Jesse Brown VAMC, Chicago, IL 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Tuccori, D. Focosi, C. Blandizzi, M. Del Tacca, and M. Petrini Re: Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized trials J Natl Cancer Inst, September 16, 2009; 101(18): 1288 - 1289. [Full Text] [PDF] L. Vidal, A. Gafter-Gvili, L. Leibovici, M. Dreyling, M. Ghielmini, and O. Shpilberg Response: Re: Rituximab Maintenance for the Treatment of Patients With Follicular Lymphoma: Systematic Review and Meta-analysis of Randomized trials J Natl Cancer Inst, September 16, 2009; 101(18): 1289 - 1290. [Full Text] [PDF] E. O. Major Reemergence of PML in Natalizumab-Treated Patients -- New Cases, Same Concerns N. Engl. J. Med., September 10, 2009; 361(11): 1041 - 1043. [Full Text] [PDF] K. L. Tyler Emerging Viral Infections of the Central Nervous System: Part 2 Arch Neurol, September 1, 2009; 66(9): 1065 - 1074. [Abstract] [Full Text] [PDF] Rituximab and Progressive Multifocal Leukoencephalopathy Journal Watch Oncology and Hematology, June 30, 2009; 2009(630): 2 - 2. [Full Text]

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