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Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation
1Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Insights
This study found that high-dose cyclophosphamide (CY) and busulfan (BU) increase hemorrhagic cystitis (HC) risk after stem cell transplantation (SCT). Prophylactic Mesna and bladder irrigation were surprisingly identified as significant risk factors for HC.
Area of Science:
- Hematology
- Oncology
- Urology
Background:
- Hemorrhagic cystitis (HC) is a significant complication following stem cell transplantation (SCT).
- Identifying risk factors and optimal prophylactic therapies for HC is crucial for patient management.
Purpose of the Study:
- To determine the most appropriate prophylactic therapy for hemorrhagic cystitis (HC) post-stem cell transplantation (SCT).
- To identify risk factors associated with the development of early- and late-onset HC.
Main Methods:
- Retrospective analysis of clinical records from 450 SCT patients treated between 1982 and 2002.
- Statistical analysis including Fisher's exact test and multivariate analysis to identify risk factors.
Main Results:
- Cyclophosphamide (CY), busulfan (BU), antithymocyte globulin, and non-radiation conditioning were associated with increased HC risk.
- Prophylactic Mesna and bladder irrigation were identified as significant risk factors for early-onset HC.
- The combination of BU and Mesna posed a greater risk than Mesna alone.
Conclusions:
- High-dose BU and CY contribute to HC development.
- Bladder irrigation, intended for protection, demonstrated an adverse effect on HC incidence.
- Mesna may possess a toxic effect on the bladder mucosa, increasing HC risk.
Abstract:
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), nonradiation (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.