Hemorrhagic cystitis--a manifestation of graft versus host disease?

In 125 allogeneic bone marrow transplant recipients conditioned with cyclophosphamide (CY) with or without total body irradiation (TBI), three different protocols for prevention of CY urotoxicity have been used. The three protocols consisted of forced alkaline diuresis alone and then in combination with mesna (sodium 2-mercaptoethane sulfonate) at a low or high dose (60-90% and 150% of the CY dose, respectively). Hemorrhagic cystitis (HC) occurred in 21 patients: there were four immediate episodes without subjective symptoms which healed within a week after starting CY and 20 late episodes, starting between 17 and 51 (median 27) days. There was no correlation between the occurrence of HC and the different protocols used for prevention of urothelial toxicity. Late HC, however, except in one patient, always appeared together with acute graft-versus-host disease (GVHD) and the severity of the HC correlated with the severity of the GVHD (p less than 0.001). When acute GVHD commenced the HC started within 24 hours in three patients and in 11 patients when the dose of prednisolone given for an ongoing GVHD was reduced. In four other patients CY was not used for conditioning, but mustargen or melphalan in combination with TBI. In this group no urothelial protection was used. One of these patients developed a severe HC together with a grade II GVHD. Adenovirus and cytomegalovirus infections were not associated with HC.