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

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2009 Mar 7

PMID 19264918

Citations 298

Authors

Kenneth R Carson

Andrew M Evens

Elizabeth A Richey

Thomas M Habermann

Daniele Focosi

John F Seymour

Jacob Laubach

Susie D Bawn

Leo I Gordon

Jane N Winter

Richard R Furman

Julie M Vose

Andrew D Zelenetz

Ronac Mamtani

Dennis W Raisch

Gary W Dorshimer

Steven T Rosen

Kenji Muro

Numa R Gottardi-Littell

Robert L Talley

Oliver Sartor

David Green

Eugene O Major

Charles L Bennett

Affiliations

Soon will be listed here.

Abstract

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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References

Kappos L, Bates D, Hartung H, Havrdova E, Miller D, Polman C . Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol. 2007; 6(5):431-41. DOI: 10.1016/S1474-4422(07)70078-9. View

Sabath B, Major E . Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy. J Infect Dis. 2002; 186 Suppl 2:S180-6. DOI: 10.1086/344280. View

Holman R, Torok T, Belay E, Janssen R, Schonberger L . Progressive multifocal leukoencephalopathy in the United States, 1979-1994: increased mortality associated with HIV infection. Neuroepidemiology. 1998; 17(6):303-9. DOI: 10.1159/000026184. View

Yokoyama H, Watanabe T, Maruyama D, Kim S, Kobayashi Y, Tobinai K . Progressive multifocal leukoencephalopathy in a patient with B-cell lymphoma during rituximab-containing chemotherapy: case report and review of the literature. Int J Hematol. 2008; 88(4):443-447. DOI: 10.1007/s12185-008-0168-2. View

Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C . Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005; 23(18):4117-26. DOI: 10.1200/JCO.2005.09.131. View

Pelosini M, Focosi D, Rita F, Galimberti S, Caracciolo F, Benedetti E . Progressive multifocal leukoencephalopathy: report of three cases in HIV-negative hematological patients and review of literature. Ann Hematol. 2007; 87(5):405-12. DOI: 10.1007/s00277-007-0411-6. View

Stasi R, Del Poeta G, Stipa E, Evangelista M, Trawinska M, Cooper N . Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood. 2007; 110(8):2924-30. DOI: 10.1182/blood-2007-02-068999. View

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R . CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346(4):235-42. DOI: 10.1056/NEJMoa011795. View

Langer-Gould A, Atlas S, Green A, Bollen A, Pelletier D . Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005; 353(4):375-81. DOI: 10.1056/NEJMoa051847. View

10.

ASTROM K, MANCALL E, Richardson Jr E . Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease. Brain. 1958; 81(1):93-111. DOI: 10.1093/brain/81.1.93. View

11.

Arnold D, Dentali F, Crowther M, Meyer R, Cook R, Sigouin C . Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007; 146(1):25-33. DOI: 10.7326/0003-4819-146-1-200701020-00006. View

12.

Berger J, Major E . Progressive multifocal leukoencephalopathy. Semin Neurol. 2000; 19(2):193-200. DOI: 10.1055/s-2008-1040837. View

13.

Weber F, Goldmann C, Kramer M, Kaup F, Pickhardt M, Young P . Cellular and humoral immune response in progressive multifocal leukoencephalopathy. Ann Neurol. 2001; 49(5):636-42. View

14.

Mehedi Hasan M, Taylor P . Progressive multifocal leucoencephalopathy in a case of chronic lymphocytic leukaemia. Br J Haematol. 2005; 130(6):808. DOI: 10.1111/j.1365-2141.2005.05587.x. View

15.

Fong I, Britton C, Luinstra K, Toma E, Mahony J . Diagnostic value of detecting JC virus DNA in cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. J Clin Microbiol. 1995; 33(2):484-6. PMC: 227972. DOI: 10.1128/jcm.33.2.484-486.1995. View

16.

Dubois V, Moret H, Lafon M, Janvresse C, Dussaix E, Icart J . Prevalence of JC virus viraemia in HIV-infected patients with or without neurological disorders: a prospective study. J Neurovirol. 1998; 4(5):539-44. DOI: 10.3109/13550289809113498. View

17.

Teramoto T, Kaneko H, Funato M, Sawa H, Nagashima K, Hirose Y . Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia. Scand J Infect Dis. 2004; 35(11-12):909-10. DOI: 10.1080/00365540310016673. View

18.

Laszlo D, Bassi S, Andreola G, Agazzi A, Antoniotti P, Balzano R . Peripheral T-lymphocyte subsets in patients treated with Rituximab-Chlorambucil combination therapy for indolent NHL. Ann Hematol. 2006; 85(11):813-4. DOI: 10.1007/s00277-006-0170-9. View

19.

Baehring J, Vives K, Bannykh S . Progressive multifocal leukoencephalopathy in a patient with marginal zone B-cell lymphoma. J Neurooncol. 2007; 85(3):289-90. DOI: 10.1007/s11060-007-9452-x. View

20.

Delbue S, Guerini F, Mancuso R, Caputo D, Mazziotti R, Saresella M . JC virus viremia in interferon-beta -treated and untreated Italian multiple sclerosis patients and healthy controls. J Neurovirol. 2007; 13(1):73-7. DOI: 10.1080/13550280601094563. View