General toxicity of cyclophosphamide in rheumatic diseases
- Megan B Clowse, MD, MPH
Megan B Clowse, MD, MPH
- Assistant Professor of Medicine
- Duke University Medical Center
- Division of Rheumatology and Immunology
- W. Joseph McCune, MD, MACR
W. Joseph McCune, MD, MACR
- Michael H and Marcia S Klein Professor of Rheumatic Diseases
- Associate Chief, Division of Rheumatology
- Director, Lupus Program
- University of Michigan
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Clinical professor, University of Washington, Seattle
- Clinical professor, University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific Arthritis Associates
Cyclophosphamide (CYC) is an alkylating agent that was introduced into clinical practice as a chemotherapeutic agent but has also been used to treat a number of systemic autoimmune diseases. It is generally used in cases of life- or organ-threatening rheumatic diseases, such as antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis or systemic lupus erythematosus (SLE) with renal or central nervous system involvement.
CYC is also associated with a variety of toxicities which should lead clinicians to consider less toxic alternative medications whenever possible. While much of our knowledge about the toxicity of CYC has been extrapolated from its use in oncology, there are important differences in dosing and duration of treatment when used to treat rheumatic diseases.
This topic will provide an overview of the mechanism of action and major toxicities associated with CYC use for the treatment of systemic rheumatic diseases. General principles of the use of CYC for rheumatic diseases as well as the pharmacology of the drug are discussed separately. (See "General principles of the use of cyclophosphamide in rheumatic diseases".)
MECHANISM OF ACTION
Alkylating agents exert their biologic activity via covalent binding and crosslinking of a variety of macromolecules including DNA, RNA, and proteins. DNA crosslinking, probably the most important biologic action of these drugs, impairs DNA replication and transcription, ultimately leading either to cell death or to altered cellular function .
The degree of inhibition of immune function is dependent upon the dose and duration of therapy. Alkylating agents are cytotoxic. Absolute lymphopenia is frequently seen following their administration, with reductions in the number of B cells and T cells of both CD4+ and CD8+ types [2,3]. The ratio of circulating T cells and B cells may also be affected .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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