Hemorrhagic Cystitis

Hemorrhagic cystitis after transplant may be caused by cyclophosphamide or ifosfamide. The nonenzymatic metabolite of these agents, acrolein, causes hyperemia and ulceration of the bladder mucosa, resulting in hemorrhage and focal necrosis. Previously treatment with busulfan appears to increase the risk of hemorrhagic cystitis.114 Prophylaxis includes hyperhydration with forced diuresis, bladder irrigation, or mesna. There is no clear preferred strategy. Randomized studies comparing one prophylactic strategy to another have had mixed results.115-119

BK polyoma virus is another cause of hemorrhagic cystitis.117'120-123 Several investigators have demonstrated the presence of BK viruria in patients undergoing transplant, not all of whom had hemorrhagic cystitis. Neither background viral reactivation nor urothelial damage explain the increase in BK viruria in patients with hemorrhagic cystitis. This data was corroborated by Bogdonovic and colleagues, who also found that the risk of hemorrhagic cystitis from BK virus was the viral load.124

Late hemorrhagic cystitis can also be caused by adenovirus. In both culture and PCR analyses, 60% and 57% of patients were positive for adenovirus, respectively. PCR was not quantitative in this study and therefore no information is available regarding the number of viral copies and extent of disease.125

Early microscopic hematuria usually resolves spontaneously. Late hemorrhagic cystitis can result in significant bleeding and pain and treatment can be problematic. A number of therapies have been reported, including bladder instillation with formalin,126 prostaglandin E1127 or alum,128 electrode fulguration,129 suprapubic cystostomy,130 and embolization of vesicle arteries.131 Several patients have been treated with intravesical antibiotics.132 Most of these reports are anecdotal, making it difficult to determine whether one is superior to another. Hemorrhagic cystitis may be more common in recipients of unrelated donor stem cells.133

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