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Late-onset neutropenia following rituximab therapy in rheumatic diseases: association with B lymphocyte depletion and infections
Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
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2011 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, no 8, 2209-2214 p.Article in journal (Refereed) Published
Abstract [en]


Late-onset neutropenia following rituximab therapy is a well-recognized side effect in lymphoma patients, but only a few cases of late-onset neutropenia have been reported in patients with autoimmune disorders. The purpose of this study was to define the incidence, clinical features, and some of the underlying mechanisms of late-onset neutropenia in relation to rituximab use in several rheumatic diseases.


We conducted a retrospective analysis of a cohort of 209 consecutive patients with rheumatic diseases who had been treated with rituximab at a university hospital between June 2003 and March 2009.


Eleven patients with late-onset neutropenia were identified. The highest incidence was observed in granulomatosis with polyangiitis (Wegener's) and systemic lupus erythematosus patients (23% and 20%, respectively), whereas the incidence in rheumatoid arthritis patients was 3%. The median time to onset of neutropenia was 102 days (range 40-362 days) and coincided with the entire period of B lymphocyte depletion; this depletion was more pronounced in patients with late-onset neutropenia (P = 0.002) than in a control group of 20 matched patients without late-onset neutropenia. Serum IgM levels decreased during the same time and to a significantly greater amount in patients with late-onset neutropenia than in controls (P = 0.027). No patient with late-onset neutropenia displayed specific antineutrophil antibodies. Seven patients were hospitalized because of infections (6 with sepsis and 1 with febrile neutropenia) that required intravenous antibiotics. Six were treated with granulocyte colony-stimulating factor.


In patients treated with rituximab for rheumatic diseases, late-onset neutropenia is a clinically significant adverse event associated with marked B lymphocyte depletion and severe infections. The incidence of late-onset neutropenia appears to vary with autoimmune disease type.

Place, publisher, year, edition, pages
2011. Vol. 63, no 8, 2209-2214 p.
National Category
Clinical Medicine
URN: urn:nbn:se:uu:diva-233812DOI: 10.1002/art.30427PubMedID: 21560117OAI: oai:DiVA.org:uu-233812DiVA: diva2:754365
Available from: 2014-10-10 Created: 2014-10-10 Last updated: 2014-10-14Bibliographically approved

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