Objective: Cyclophosphamide (CPA)-induced hemorrhagic cystitis is sometimes difficult to manage. We investigated the mucosal changes in patients subjected to CPA therapy in relation to the duration and accumulating dose of CPA. Methods: Fifteen patients, all of whom were receiving CPA, were studied. Investigation of the dose and duration of CPA administration, urinalysis and cystoscopy was performed. Results: The total doses of CPA administered ranged from 2.5 to 237.0 g, and the duration of administration ranged from 4 to 130 months. Four patients with hematuria (micro or macro) showed various degrees of mucosal hyperemia and telangiectasia. Of 11 patients without microhematuria, 6 patients also revealed mucosal changes distinctive of CPA-induced hemorrhagic cystitis. CPA-induced cystitis with no hematuria insidiously progressed in the patients who received CPA orally at a total dose of more than 40 g and/or for longer than 36 months. Conclusion: Early mucosal lesion of the urinary bladder, which will most likely be followed by CPA-induced hemorrhagic cystitis, may develop prior to the appearance of microscopic hematuria. Periodic prophylactic cystoscopy is recommend in patients receiving CPA.

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