This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Weiner, H L Articles by Cohen, J A Search for Related Content PubMed PubMed Citation Articles by Weiner, H L Articles by Cohen, J A Social Bookmarking                         What's this?

Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects

Multiple Sclerosis Center, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, 333 Longwood Avenue, Boston, Massachusetts 02115, USA, hweiner{at}rics.bwh.harvard.edu

J A Cohen

Cleveland Clinic Foundation, The Mellen Center U10, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA

Cyclophosphamide is an alkylating agent used to treat malignancies and immune-mediated inflammatory non-malignant processes such as lupus nephritis and immune-mediated neuropathies. It has been studied as a treatment for multiple sclerosis (MS) for the past 30 years and is used by physicians in selected cases of progressive or worsening MS. Review of published reports suggests that it is efficacious in cases of worsening MS that have an inflammatory component as evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic resonance imaging (MRI) or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the central nervous system (CNS). There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. Although a general immunosuppressant that affects both T- and B-cell function, cyclophosphamide has selective immune effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects include nausea, alopecia, infertility, bladder toxicity and risk of malignancy. The most commonly used regimens involve every 4- to 8-week outpatient IV pulse therapy given with or without corticosteroids and are usually well-tolerated by patients. Cyclophosphamide is currently used in patients whose disease is not controlled by beta-interferon or glatiramer acetate and those with rapidly worsening MS.

Key Words: cyclophosphamide • immunotherapy • multiple sclerosis • review

Multiple Sclerosis, Vol. 8, No. 2, 142-154 (2002)
DOI: 10.1191/1352458502ms790oa


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Krishnan, A. I. Kaplin, R. A. Brodsky, D. B. Drachman, R. J. Jones, D. L. Pham, N. D. Richert, C. A. Pardo, D. M. Yousem, E. Hammond, et al. Reduction of Disease Activity and Disability With High-Dose Cyclophosphamide in Patients With Aggressive Multiple Sclerosis Arch Neurol, August 1, 2008; 65(8): 1044 - 1051. [Abstract] [Full Text] [PDF]

				D R Smith, B Weinstock-Guttman, J A Cohen, X Wei, C Gutmann, R Bakshi, M Olek, L Stone, S Greenberg, D Stuart, et al. A randomized blinded trial of combination therapy with cyclophosphamide in patients with active multiple sclerosis on interferon beta Multiple Sclerosis, October 1, 2005; 11(5): 573 - 582. [Abstract] [PDF]

				E. M. Frohman, O. Stuve, E. Havrdova, J. Corboy, A. Achiron, R. Zivadinov, P. S. Sorensen, J. T. Phillips, B. Weinshenker, K. Hawker, et al. Therapeutic Considerations for Disease Progression in Multiple Sclerosis: Evidence, Experience, and Future Expectations Arch Neurol, October 1, 2005; 62(10): 1519 - 1530. [Abstract] [Full Text] [PDF]

				H Zephir, J de Seze, K Dujardin, G Dubois, M Cabaret, S Bouillaguet, D Ferriby, T Stojkovic, and P Vermersch One-year cyclophosphamide treatment combined with methylprednisolone improves cognitive dysfunction in progressive forms of multiple sclerosis Multiple Sclerosis, June 1, 2005; 11(3): 360 - 363. [Abstract] [PDF]

				P. A. Muraro, D. C. Douek, A. Packer, K. Chung, F. J. Guenaga, R. Cassiani-Ingoni, C. Campbell, S. Memon, J. W. Nagle, F. T. Hakim, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients J. Exp. Med., March 7, 2005; 201(5): 805 - 816. [Abstract] [Full Text] [PDF]

				D. R. Jeffery and R. Herndon Review of mitoxantrone in the treatment of multiple sclerosis Neurology, December 28, 2004; 63(12_suppl_6): S19 - S24. [Abstract] [Full Text]

				S. A. Rizvi and K. Bashir Other therapy options and future strategies for treating patients with multiple sclerosis Neurology, December 28, 2004; 63(12_suppl_6): S47 - S54. [Abstract] [Full Text]

				H. L. Weiner Multiple Sclerosis Is an Inflammatory T-Cell-Mediated Autoimmune Disease Arch Neurol, October 1, 2004; 61(10): 1613 - 1615. [Full Text] [PDF]

				E Portaccio, V Zipoli, G Siracusa, S Piacentini, S Sorbi, and M P Amato Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort Multiple Sclerosis, October 1, 2003; 9(5): 446 - 450. [Abstract] [PDF]

				R. K. Burt, B. A. Cohen, E. Russell, K. Spero, A. Joshi, Y. Oyama, W. J. Karpus, K. Luo, B. Jovanovic, A. Traynor, et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores Blood, October 1, 2003; 102(7): 2373 - 2378. [Abstract] [Full Text] [PDF]