Presence of mucosal change in the urinary bladder in nonhematuric patients with long-term exposure and/or accumulating high-dose cyclophosphamide. Possible significance of follow-up cystoscopy on preventing development of cyclophosphamide-induced hemorrhagic cystitis

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.Fifteen patients, all of whom were receiving CPA, were studied. Investigation of the dose and duration of CPA administration, urinalysis and cystoscopy was performed.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.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.