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Dr. J. Egido, Servicio de Nefrología, Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, E-28040 Madrid (Spain) Dear Sir, Bladder toxicity is a serious side effect of cyclophosphamide therapy. Not only can acute hemorrhagic cystitis develop [1], but later bladder fibrosis and carcinoma have been noted [2]. Bladder cancer has been reported mainly in patients who received cyclophosphamide for neoplastic diseases [4, 5], but several patients had a non-neoplastic underlying disorder [6-9]. We report the case of a patient who developed a transitional cell bladder cancer 19 years after receiving low-dose cyclosphosphamide for lupus nephritis. A 51-year-old woman had systemic lupus erythematosus diagnosed in 1967. Manifestations included arthritis, diffuse proliferative glomerulonephritis, pericarditis and central nervous system symptoms. She was treated with corticosteroids, chlorambucil, azathio-prine and chloroquine. From December 1970 to September 1971, she received a total dose of 14 g of cyclophosphamide without any evidence of cystitis, but the drug was discontinued because of poor hematological tolerance. In 1990, she complained of a 3-month history of dysuria, polaquiuria and lumbar pain. Immunosuppressive medication at this time consisted of azathioprine 50 mg/day, and creatinine clearance was 50 ml/min. A renal ultrasound disclosed right-side hydro-nephrosis. Cystoscopy revealed a bladder tumor. Biopsy specimens showed poorly differentiated transitional cell carcinoma with squamous metaplasia (fig. 1). She underwent total cystectomy with ureterosigmoidostomy. There were no other risk factors for bladder cancer. Fig. 1. Transitional cell carcinoma invading smooth muscle of bladder. HE. Bladder cancer associated with cyclosphosphamide was first noted in 1971 [3]. Since then, at least 65 cases have been reported in the world literature [4-6]. Four of these had underlying systemic lupus erythematosus and 1 was a renal transplant recipient [7-9]. The relative risk of bladder cancer in patients with malignancy has been estimated to be 6.8-7.9 [4, 5], and there is no apparent plateau for the cumulative risk curve, indicating that the risk may increase further with time [4]. There is much less information about bladder cancer in patients with benign diseases, and controlled studies are needed. The total cyclophosphamide dose associated with cancer has been as low as 3.8 g, although usually it exceeds 100 g [6, 9], Cyclophosphamide was maintained from a few days, as in the case of