Twenty-four patients with severe progressive rheumatoid arthritis were randomly assigned to cyclophosphamide or placebo in a double-blind crossover trial.Eleven patients who completed 9 months on cycloplosphamide (average dose: 1.8 mg/ kg/day) demonstrated significant decrease in painful joints, swollen joints, and moroing stiffness and increase in grip strength when compared to 11 patients on placebo. After crossover, significant improvement was observed in patients switched to cyclophosphamide, and deterioration within 2 months was observed in most patients changed from drug to placebo. Serum immunoglobulins and rheumatoid factor titers decreased with cyclophosphamide but antibody response to Vi antigen was unaffected. Primary delayed immune response to 2,4-dinitrochlorobenzene was markedly depressed. Adverse effects were troublesomehemorrhagic cystitis affected 4 patients and amenorrhea occurred in 3. Despite its striking beneficial effect, cyclophosphamide

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Love, R. R., and Sowa, J. M. (1975). Annals of the Rheumatic Diseases, 34, 534-535. Myelomonocytic leukaemia following cyclophosphamide therapy of rheumatoid disease. A 69-year-old woman treated for 31 months with daily oral cyclophosphamide for refractory rheumatoid disease developed acute myelomonocytic leukaemia 24 years after stopping the drug. The possibility of a causal association between the therapy and subsequent leukaemia is supported by the growing experience with cytotoxic agents.