Factors Associated with More Severe BK Hemorrhagic Cystitis in an Allogeneic Hematopoietic Cell Transplant Cohort

Background BK polyoma virus (BKPyV) has been associated with hemorrhagic cystitis (HC) after hematopoietic cell transplant (HCT). Prior studies have examined risk factors for BKPyV-associated HC, but have been limited by inclusion of pre-engraftment hemorrhagic cystitis or cases without macroscopic hemorrhage. Few studies have examined factors associated with the clinical course of BKPyV-HC. Methods We retrospectively analyzed allogeneic HCT recipients transplanted between 2007-2017, and included all patients with BKPyV-HC (defined as macroscopic hematuria [Bedi grade >/=2] and positive urine BKPyV PCR who had at least one available plasma BKPyV viral load sample after platelet engraftment or day 28 post-HCT. Duration was determined by time to resolution of hematuria and symptoms. Demographic, transplant, viral, and immune characteristics were investigated in multivariable models using time-varying covariates to determine factors associated with resolution of macroscopic hematuria, resolution of overall symptoms, need for continuous bladder irrigation (CBI) or surgical intervention, need for transfusion, or development of clots by day 90 after diagnosis. Results BKPyV-HC developed in 128 allogeneic HCT recipients (70% myeloablative conditioning) at a median of 58 days post-transplant (IQR 46 – 78) and the median time to symptom resolution was 23.5 days (15 - 44). Mortality by day 90 post-BKPyV-HC diagnosis was 20% [26/128]. Plasma viral load >/=10,000 at presentation was associated with both longer duration of macroscopic hematuria and longer duration of overall symptoms [aHRs for resolution 0.31 (95% CI 0.11, 0.91), 0.32 (95% CI 0.11, 0.95), respectively], but not associated with need for continuous bladder irrigation or surgical intervention [HR 1.15 (95% CI 0.42, 3.14)], development of clots [HR 1.31 (95% CI 0.50, 3.46)], or need for transfusion during their course [HR 1.62 (95% CI 0.44, 5.99)]. Absolute lymphocyte count Conclusion Both immune and viral characteristics were associated with a longer duration of BKPyV-associated HC. BKPyV-associated HC is a morbid disease in need of improved management strategies; accurate descriptions of disease severity and factors associated with prolonged recovery will inform end points of future clinical trials.