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Background: Hemorrhagic cystitis (HC) is a frequent complication after HSCT and can significantly affect the patient's quality of life. BK virus (BKV), chemotherapy, irradiation, and graft versus host disease (GVHD) have been associated with the pathogenesis of HC. To investigate the relationship of HC and BKV, we prospectively evaluated patient's BKV pre-HSCT serology and BKV in the urine, and the association between BKV viruria and HC.
Methods: From April 2010 through October 2011, we prospectively followed 98 adult HSCT patients. The patients were monitored for BKV in the urine by quantitive polymerase chain reaction (Q-PCR) every 2 weeks from start of conditioning until 15 weeks post-HSCT. Pre-HSCT BKV IgG titers were measured by ELISA. All tests were performed by Viracor-IBT Laboratories. BKV viruria was defined as: ≥1 Q-PCR assay of >500 copies/mL; PEAK: ≥3-log increase in BKV Q-PCR from pre-HSCT Q-PCR. A chart review was performed to determine the development of HC. HC was graded according to Bedi et al and was considered significant if ≥ grade 2. Ciprofloxacin use was included from day -14 through day +14 post-transplant. Competing regression was performed using clinical characteristics and urine BKV PCRs to identify risk factors for development of HC.
Results: The median age of the patients was 52 years (range 20-73), 60% were male, 49% of patients underwent myeloablative conditioning, 50% received T-cell depleted, and 21% cord blood grafts. Acute grade 2-3 GVHD was diagnosed in 32% of patients and 31% had received Keratinocyte growth factor (KGF) pretransplant. All patients (100%) were BKV IgG positive pretransplant. By day 0, the cumulative incidence (CI) of BKV viruria was 22%. By day+30, the CI was 50% and it remained stable thereafter for the duration of the study. The CI rates for BKV were similar among different stem cell sources. Ten patients (10%) patients developed HC at a median 40 days post transplant (range 0-146) and 7/10 (70%) patients with HC had BKV (2 with concomitant adenovirus). Risk factors for HC were older age (P=0.004), and BK viruria ≥107 copies/mL either pre- (P=0.001) or post-HSCT (P=0.005). One of 30 patients (3%) who received KGF developed HC and 9 of 68 patients (13%) who did not receive KGF developed HC (P=0.175). One of 35 patients (3%) who received ciprofloxacin developed HC and 9 of 63 patients (14%) who did not receive ciprofloxacin developed HC (P=0.091). During the study period, 36 patients died and 8 patients had autopsies performed. One of the 8 patients was found to have BKV nephropathy at autopsy.
Conclusions: 1) In this study, the incidence of BK viruria was not significantly different among various stem cell sources. 2) High level BK viruria (≥107 copies/mL) and older age were significant predictors of HC. 3) While BK viruria was frequent (50%) during the study period, the rate of HC was low (10%) suggesting additional co-factors in the pathogenesis of HC.
