Study Looks at Risk of Bladder Injury in Children Undergoing a Stem Cell Transplant

CHOP Attending Nephrologist, Benjamin Laskin, MD, MS, was recently awarded a five-year R01 research study from the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. The study will examine bladder injury in children undergoing a stem cell transplant. Hemorrhagic cystitis — or bleeding from the bladder — occurs in up to 25% of stem cell transplant recipients and is associated with BK polyomavirus (BKPyV) infection, although the exact cause of the bladder injury is not known. BKPyV infects most people in the general population but remains dormant in the cells of the kidney and bladder, reactivating to cause disease in patients who are receiving immunosuppression, such as after transplant.

Hemorrhagic cystitis leads to patient morbidity from painful urination, prolonged hospitalizations, increased blood transfusion requirements, and invasive procedures when urinary obstruction is present. Each episode of hemorrhagic cystitis accounts for 10 additional hospital days and costs $70,000. In its most severe presentation, hemorrhagic cystitis may be associated with a higher risk of death. BKPyV replication in the urine can be detected in 80% of patients after stem cell transplant, but not all of these patients will develop hemorrhagic cystitis. There are no antiviral therapies with proven efficacy against BKPyV and current treatment strategies for hemorrhagic cystitis are limited to supportive care.

For the study, Dr. Laskin is collaborating with the stem cell transplant teams at CHOP and Cincinnati Children’s Hospital Medical Center, as well as virologists at the University of Cincinnati. The team is studying samples from an established patient repository at the two centers, and they are also enrolling an additional 200 children undergoing stem cell transplant to validate the findings.

The proposed research project will test the hypothesis that the risk of hemorrhagic cystitis in patients with BKPyV replication in the urine is due to the specific viral strain and the patient’s response to the virus. Specifically, the team will test whether the strain of BKPyV is different between patients with and without hemorrhagic cystitis after stem cell transplant. Using proteomics techniques, they will also test whether a patient’s cellular response to the virus is different between those with and without hemorrhagic cystitis.

The study’s results are expected to increase our understanding of the mechanisms of bladder injury after stem cell transplant. However, other transplant recipients, including those after kidney transplant, are at risk for kidney and bladder disease from BKPyV.

Therefore, the knowledge gained will also hopefully improve care for other high-risk patients. The research will provide the foundation for future clinical trials testing if strategies such as the infusion of virus fighting T-cells can prevent or treat BKPyV polyomavirus-associated disease and subsequently decrease morbidity and mortality for transplant patients.