Symptomatic Improvement Following Intravesicular Cidofovir for the Management of BK Virus Associated Cystitis.

Abstract

BACKGROUND: Hemorrhagic cystitis (HC) is a complication of hematopoietic stem cell transplantation, occurring in 10 to 70% of transplant recipients. Factors that may contribute to the risk of developing HC include intensive preparative regimens, especially those including busulfan, high-dose cyclophosphamide or ifosfamide, transplantation from matched unrelated donors, infection with adenovirus, and the development of graft-versus-host disease. The reactivation of latent BK virus in the kidney is thought to lead to the development of late-onset HC in hematopoietic stem cell transplant patients. Early reports of cidofovir's efficacy in BK virus-associated HC used intravenous cidofovir, but treatment was often complicated or compromised by excessive toxicity, especially renal compromise. Based on small single patient reports of the use of intravesicular cidofovir in the management of other viral causes of cystitis, we evaluated the use of intravesicular cidofovir for the management of BK virus associated cystitis.METHODS: In patients undergoing stem cell transplant, BK viral loads were routinely monitored twice weekly. The presence of cystitis or hematuria in a patient with detectable BK viruria was considered the trigger for initiation of therapy. Patients were treated with cidofovir at a dose of 5 mg/kg. Drug was diluted with 60mL of normal saline and administered via foley catheter, which was clamped for one hour post administration. Weekly repeat dosing was allowed as long as symptoms persisted. In addition to symptom control, BK viral loads were measured before, during, and after treatment.RESULTS: Four patients were included in this initial evaluation. All were recipients of allogeneic stem cell transplants; three were recipients of matched unrelated donor transplants and one received a transplant from a matched sibling. Patients received between 1 and 4 doses of cidofovir for initial therapy. All 4 patients experienced complete resolution of symptoms. The range for symptom resolution ranged from 2 days to 3 weeks. Symptoms reappeared in only 1 patient after discontinuation of therapy. Monitoring of BK urine viral loads revealed that 3 of the 4 patients had a greater than 50% decrease in urine BK viral load with initial dosing of cidofovir, indicating presence of antiviral activity when the drug is administered by this novel route.CONCLUSION: Intravesicular cidofovir is safe, easy to administer, and associated with both elimination of symptoms and reduction in viral loads in patients with hemorrhagic cystitis following high dose therapy and allogeneic transplantation.