Acute leukemia in rheumatoid arthritis treated with cytotoxic agents

Acute leukemia is described in two patients treated with cytotoxic agents for a destructive, seropositive rheumatoid arthritis. Both patients had received longterm azathioprine therapy. In addition, one patient had been treated with cyclophosphamide, the other with melphalan. Chromosomal abnormalities were noted in both patients. Studies in one patient included colony forming units, ferrokinetics, electron microscopy of bone marrow, and autopsy examination. All reports of acute leukemia associated with cytostatic drugs in the literature to date are reviewed and the possible mechanisms discussed. It is suggested that patients with rheumatoid arthritis treated with azathioprine and alkylating agents may have an increased risk of developing a therapy-related acute leukemia.