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Effective Suppression of Cerebrospinal Fluid B Cells by Rituximab and Cyclophosphamide in Progressive Multiple Sclerosis

Effective Suppression of Cerebrospinal Fluid B Cells by Rituximab and Cyclophosphamide in... In the February issue of the ARCHIVES, Monson et al1 reported on a small series of cases of patients with primary progressive multiple sclerosis (MS) treated with rituximab. Analyzing the cerebrospinal fluid (CSF) B cell counts in 2 of them, they concluded that rituximab depleted CSF B cells to a lesser degree than peripheral blood B cells. Here we communicate our observations in a patient with relapsing-remitting MS who responded to a combined treatment regimen consisting of rituximab and cyclophosphamide. The 19-year-old man presented with a third attack within a year. The diagnosis was ascertained according to the McDonald criteria with typical findings on CSF analysis and magnetic resonance imaging. Interferon-β treatment was initiated, but he continued relapsing. Despite initiation of cyclophosphamide pulse therapy, the patient deteriorated to complete tetraplegia and required mechanical ventilation. At that point, we decided to give him 4 courses of rituximab at 375 mg/m2 in weekly intervals whereon he gradually recovered. The number of B cells in native CSF and peripheral blood was determined by flow cytometry using monoclonal phycoerythrin-labeled anti-CD19 and anti-CD20 antibodies before the first, second, third, and fourth course of rituximab. In addition, peripheral B cells were measured 3 months after initiation of rituximab. Before treatment, the total B cell count in the CSF was 3% and consecutively dropped to 0.25%, 0%, and 0%. In the peripheral blood, the B cell count was 5.3% before treatment and dropped to 0% during follow-up. These findings illustrate that rituximab has the potential to deplete B cells from the CSF as rapidly as from peripheral blood. However, the kinetics and the favorable treatment response observed in our case might be attributed to the concomitant treatment with cyclophosphamide, according to a study recently published on patients with rheumatoid arthritis where a synergistic effect of rituximab and cyclophosphamide or methotrexate was observed.2 Peripheral B cell depletion in these patients was observed for up to 48 weeks; however, no data are currently available about the duration of B cell depletion in CSF on combination therapy in patients with MS. Our observations support the view that B cells may represent an attractive therapeutic target in patients with severe MS and that further studies are warranted. Back to top Article Information Correspondence: Dr Petereit, Department of Neurology, University of Cologne, Kerpener Strasse 62, 50924 Köln, Germany (hela.petereit@medizin.uni-koeln.de). References 1. Monson NLCravens PDFrohman EMHawker KRacke MK Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol200562258264PubMedGoogle Scholar 2. Edwards JCWSzczepanski LSzechinski J et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;3502572- 2581PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Effective Suppression of Cerebrospinal Fluid B Cells by Rituximab and Cyclophosphamide in Progressive Multiple Sclerosis

Petereit, Hela-F; Rubbert, Andrea
Archives of Neurology , Volume 62 (10) – Oct 1, 2005
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Effective Suppression of Cerebrospinal Fluid B Cells by Rituximab and Cyclophosphamide in Progressive Multiple Sclerosis

Abstract

In the February issue of the ARCHIVES, Monson et al1 reported on a small series of cases of patients with primary progressive multiple sclerosis (MS) treated with rituximab. Analyzing the cerebrospinal fluid (CSF) B cell counts in 2 of them, they concluded that rituximab depleted CSF B cells to a lesser degree than peripheral blood B cells. Here we communicate our observations in a patient with relapsing-remitting MS who responded to a combined treatment regimen consisting of rituximab and...
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Publisher
American Medical Association
Copyright
Copyright © 2005 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.62.10.1641-b
Publisher site
See Article on Publisher Site

Abstract

In the February issue of the ARCHIVES, Monson et al1 reported on a small series of cases of patients with primary progressive multiple sclerosis (MS) treated with rituximab. Analyzing the cerebrospinal fluid (CSF) B cell counts in 2 of them, they concluded that rituximab depleted CSF B cells to a lesser degree than peripheral blood B cells. Here we communicate our observations in a patient with relapsing-remitting MS who responded to a combined treatment regimen consisting of rituximab and cyclophosphamide. The 19-year-old man presented with a third attack within a year. The diagnosis was ascertained according to the McDonald criteria with typical findings on CSF analysis and magnetic resonance imaging. Interferon-β treatment was initiated, but he continued relapsing. Despite initiation of cyclophosphamide pulse therapy, the patient deteriorated to complete tetraplegia and required mechanical ventilation. At that point, we decided to give him 4 courses of rituximab at 375 mg/m2 in weekly intervals whereon he gradually recovered. The number of B cells in native CSF and peripheral blood was determined by flow cytometry using monoclonal phycoerythrin-labeled anti-CD19 and anti-CD20 antibodies before the first, second, third, and fourth course of rituximab. In addition, peripheral B cells were measured 3 months after initiation of rituximab. Before treatment, the total B cell count in the CSF was 3% and consecutively dropped to 0.25%, 0%, and 0%. In the peripheral blood, the B cell count was 5.3% before treatment and dropped to 0% during follow-up. These findings illustrate that rituximab has the potential to deplete B cells from the CSF as rapidly as from peripheral blood. However, the kinetics and the favorable treatment response observed in our case might be attributed to the concomitant treatment with cyclophosphamide, according to a study recently published on patients with rheumatoid arthritis where a synergistic effect of rituximab and cyclophosphamide or methotrexate was observed.2 Peripheral B cell depletion in these patients was observed for up to 48 weeks; however, no data are currently available about the duration of B cell depletion in CSF on combination therapy in patients with MS. Our observations support the view that B cells may represent an attractive therapeutic target in patients with severe MS and that further studies are warranted. Back to top Article Information Correspondence: Dr Petereit, Department of Neurology, University of Cologne, Kerpener Strasse 62, 50924 Köln, Germany (hela.petereit@medizin.uni-koeln.de). References 1. Monson NLCravens PDFrohman EMHawker KRacke MK Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol200562258264PubMedGoogle Scholar 2. Edwards JCWSzczepanski LSzechinski J et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;3502572- 2581PubMedGoogle ScholarCrossref

Journal

Archives of Neurology – American Medical Association

Published: Oct 1, 2005

Keywords: b-lymphocytes,cyclophosphamide,multiple sclerosis,cerebrospinal fluid,rituximab,psychological suppression

References

  • Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis.
    Racke MK; Arch Neurol
  • Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.
    Szechinski J; N Engl J Med