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. 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 Marie Vose, Andrew D. Zelenetz, Ronac Mamtani, Dennis W. Raisch, Gary W. Dorshimer, Steven T. Rosen, Kenji Muro, Numa R. Gottardi-Littell, Robert L. Talley & 4 others Oliver Sartor, David Green, Eugene O. Major, Charles L. Bennett

Research output: Contribution to journalArticle

674 Citations (Scopus)

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 PMLafter 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 PMLafter 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.

Original languageEnglish (US)
Pages (from-to)4834-4840
Number of pages7
JournalBlood
Volume113
Issue number20
DOIs
StatePublished - Nov 17 2009

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Progressive Multifocal Leukoencephalopathy
Drug-Related Side Effects and Adverse Reactions
HIV
Research
Pharmaceutical Preparations
Therapeutics
Pancytopenia
Lymphoproliferative Disorders
Adrenal Cortex Hormones
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Rituximab
Alkylating Agents
Azathioprine
Stem cells
Autoimmune Hemolytic Anemia
Idiopathic Thrombocytopenic Purpura
Hematopoietic Stem Cell Transplantation
Proxy
United States Food and Drug Administration

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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. / Carson, Kenneth R.; Evens, Andrew M.; Richey, Elizabeth A.; Habermann, Thomas M.; Focosi, Daniele; Seymour, John F.; Laubach, Jacob; Bawn, Susie D.; Gordon, Leo I.; Winter, Jane N.; Furman, Richard R.; Vose, Julie Marie; Zelenetz, Andrew D.; Mamtani, Ronac; Raisch, Dennis W.; Dorshimer, Gary W.; Rosen, Steven T.; Muro, Kenji; Gottardi-Littell, Numa R.; Talley, Robert L.; Sartor, Oliver; Green, David; Major, Eugene O.; Bennett, Charles L.

In: Blood, Vol. 113, No. 20, 17.11.2009, p. 4834-4840.

Research output: Contribution to journalArticle

Carson, KR, Evens, AM, Richey, EA, Habermann, TM, Focosi, D, Seymour, JF, Laubach, J, Bawn, SD, Gordon, LI, Winter, JN, Furman, RR, Vose, JM, Zelenetz, AD, Mamtani, R, Raisch, DW, Dorshimer, GW, Rosen, ST, Muro, K, Gottardi-Littell, NR, Talley, RL, Sartor, O, Green, D, Major, EO & Bennett, CL 2009, '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', Blood, vol. 113, no. 20, pp. 4834-4840. https://doi.org/10.1182/blood-2008-10-186999
Carson, Kenneth R. ; Evens, Andrew M. ; Richey, Elizabeth A. ; Habermann, Thomas M. ; Focosi, Daniele ; Seymour, John F. ; Laubach, Jacob ; Bawn, Susie D. ; Gordon, Leo I. ; Winter, Jane N. ; Furman, Richard R. ; Vose, Julie Marie ; Zelenetz, Andrew D. ; Mamtani, Ronac ; Raisch, Dennis W. ; Dorshimer, Gary W. ; Rosen, Steven T. ; Muro, Kenji ; Gottardi-Littell, Numa R. ; Talley, Robert L. ; Sartor, Oliver ; Green, David ; Major, Eugene O. ; Bennett, Charles L. / 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. In: Blood. 2009 ; Vol. 113, No. 20. pp. 4834-4840.
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AU - Habermann, Thomas M.

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AU - Seymour, John F.

AU - Laubach, Jacob

AU - Bawn, Susie D.

AU - Gordon, Leo I.

AU - Winter, Jane N.

AU - Furman, Richard R.

AU - Vose, Julie Marie

AU - Zelenetz, Andrew D.

AU - Mamtani, Ronac

AU - Raisch, Dennis W.

AU - Dorshimer, Gary W.

AU - Rosen, Steven T.

AU - Muro, Kenji

AU - Gottardi-Littell, Numa R.

AU - Talley, Robert L.

AU - Sartor, Oliver

AU - Green, David

AU - Major, Eugene O.

AU - Bennett, Charles L.

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