In patients with rheumatoid arthritis and scleroderma, the frequency of major chromosome abnormalities was appreciably increased by prolonged therapy with cyclophosphamide. Metaphases from 8 patients with rheumatoid arthritis, receiving this cytotoxic drug (0.5-2.0 mg/kg/day), showed a significantly greater frequency in hypodiploidy and chromosome type breaks than a comparable control series. In addition, 5 patients with scleroderma were studied before and after the administration of cyclophosphamide and a significant increase in the number of cytogenetic aberrations was observed during therapy.The alkylating agent cyclophosphamide appears to be an effective therapeutic agent in certain connective tissue disorders in-
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