title: 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.
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.
authors.affiliation: Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Carson
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Richey
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Daniele
authors.initials: D
authors.lastname: Focosi
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.forename: Susie D
authors.initials: SD
authors.lastname: Bawn
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: Ronac
authors.initials: R
authors.lastname: Mamtani
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Gary W
authors.initials: GW
authors.lastname: Dorshimer
authors.forename: Steven T
authors.initials: ST
authors.lastname: Rosen
authors.forename: Kenji
authors.initials: K
authors.lastname: Muro
authors.forename: Numa R
authors.initials: NR
authors.lastname: Gottardi-Littell
authors.forename: Robert L
authors.initials: RL
authors.lastname: Talley
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab