Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation

To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early = 29, late = 48, both = 4). For the incidence of early- onset HC, administration of cyclophosphamide (CY) (P = 0.0079, odds ratio (OD) = 5.109, 95% confidence interval (CI) = 1.533-17.030), busulfan (BU) (P = 0.0015, OD = 3.336, 95% CI = 1.584-7.027), BU + CY (P = 0.0001, OD = 4.369, 95% CI = 2.055-9.292), antithymocyte globulin (P = 0.0009, OD = 3.368, 95% CI = 1.642-6.911), non-radiation (P = 0.0163, OD = 2.564, 95% CI = 0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (P = 0.0001, OD = 7.519, 95% CI = 2.847-19.858), and bladder irrigation (P = 0.0001, OD = 4.950, 95% CI = 2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P < 0.001) than Mesna alone (P = 0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (P = 0.0105, OD = 5.301, 95% CI = 1.477-19.026) and bladder irrigation (P = 0.0001, OD = 9.469, 95% CI = 3.872-23.156) were significant risk factors of early- onset HC. We conclude that (i) high-dose BU as well as CY is a cause of HC,(ii) protective bladder irrigation has an opposite effect, and (iii) Mesna possibly has a toxic effect on bladder mucosa.