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Hemorrhagic cystitis is associated with mortality following pediatric stem cell transplantation in a single institution retrospective cohort study
Meghan F. Davis, MD, MPH1, Briony K. Varda, MD, MPH2, Teresa L. Russell, MS2, Jacob C. Smith, MD2, M. Sohel Rana, MBBS, MPH2, Anant Vatsayan, MD2, Aaron J. Krill, MD2.
1MedStar Georgetown University Hospital, Washington, DC, USA, 2Children's National Hospital, Washington, DC, USA.

BACKGROUND: The temporal association between the development of hemorrhagic cystitis (HC) following pediatric stem cell transplant (SCT) and death is not known, yet may have implications for the selection of therapeutic interventions and counseling. The objective of this study was to use survival analysis to investigate the adjusted association between HC and mortality among children after SCT.
METHODS: A retrospective, single-center cohort study of all patients undergoing SCT between 2006 and 2020 was performed. Demographic and clinical information was collected. Survival analysis was performed and stratified by HC versus no HC. Cox Proportional-Hazards regression was used to assess the association of HC with the probability of death over time. A sub-group analysis for 1-year mortality was also performed.
RESULTS: 523 children underwent SCT during the study period. The mean age at SCT was 8 years (SD 6). A majority were male (56%) and had a single SCT (73%). Underlying diagnostic categories were split across hematologic malignancies, solid tumors and non-malignant etiologies (30%, 38% and 32%, respectively). A minority developed HC (9%), 13 of whom had grade IV HC. Patients with HC were older (11 vs 8 years old, p <0.01) and had higher unrelated donor (52% vs. 35%, p <0.01) and hematologic malignancy rates (59% vs. 27%, p<0.001). Nine patients with grade IV HC underwent surgical intervention.
Median follow up for HC and no HC was 1.2 (range: 0.001-6.2 years) and 2.9 years (range: 0.001-15.1 years), respectively. Overall, 33% of patients expired. Half of patients with HC expired (53%) compared to a third of non-HC patients (31%). Among patients with HC, the death rate was highest for grade IV HC (69%). A larger proportion of children <5 years old, with >1 SCT, a non-related donor SCT and underlying malignant diagnoses also expired. The figure shows survival time stratified by HC vs. non-HC. Median survival was 2 years for those with HC vs 14.5 years for those without. After adjusted analysis, HC was associated with a 70% higher likelihood of death (OR 1.7 [1.1-2.7], p = 0.014), and a non-malignant underlying diagnosis was protective (OR 0.5, p = 0.001). Age, gender, >1 SCT, donor type, and solid tumors were not significantly associated. Overall mortality in operative patients was 78%. A sub-group analysis of death within the first year of SCT did not show an association with HC (1.7 [0.9-3.3], p = 0.113).
CONCLUSIONS: HC occurs in a minority of pediatric patients following SCT. When it does occur, it is associated with a nearly two-fold increase in mortality with a median survival of 2 years. In cases of severe HC, a majority expire.
Figure 1. Survival probability following bone marrow transplantation for patients who did and did not develop hemorrhagic cystitis


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