Cyclophosphamide has been used since the 1960s to treat severe manifestations of autoimmune inflammatory diseases such as systemic lupus erythematosus, systemic vasculitis, and systemic sclerosis (scleroderma)(1–4). This alkylating agent, which is considered to be the “strongest” medication commonly used by rheumatologists, has well-established efficacy in lupus nephritis and systemic necrotizing vasculitis, conditions for which it became regarded as the standard of care by the 1980s (1, 2, 5). Cyclophosphamide continues to be used regularly, in clinical practice and in clinical trials, to treat other severe manifestations of lupus, lung disease in scleroderma, many types of vasculitis, and other systemic inflammatory diseases (4, 6–9). Despite the development of and interest in other agents to treat severe inflammatory disease, cyclophosphamide is unlikely to be consigned to the status “of historic interest only” any time soon.

Although the doses of cyclophosphamide prescribed in autoimmune diseases are lower than the doses typically prescribed for cancer chemotherapy, in rheumatic diseases the drug is often used for extended periods of time and, due to a high rate of clinical relapse, treatment often requires repeated courses. Cyclophosphamide resembles many other chemotherapeutic