Pilot study of early BK polyomavirus in the urine and risk of hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

BACKGROUND: BK polyomavirus (BKPyV)-associated hemorrhagic cystitis occurs in 7-60% of allogeneic hematopoietic cell transplantation (HCT) recipients and may cause significant morbidity. OBJECTIVE: We conducted a pilot study to assess if early BKPyV viruria (≤day [D]+40 post-HCT) predicted risk for BKPyV hemorrhagic cystitis in the first year post-HCT. STUDY DESIGN: Adult consecutive allogeneic HCT recipients at Memorial Sloan Kettering Cancer Center from August 2019 through April 2021 were screened for urine BKPyV quantitative PCR (Eurofins Viracor, Lenexa, KS) between D-14 and D0 (pre-HCT). If the pretransplant test was negative, urine BKPyV was retested between D+20 and D+40 postengraftment. If the pre-HCT test was positive, repeat postengraftment testing was not performed. Patients with early BKPyV viruria were monitored by plasma BKPyV quantitative PCR bimonthly for the first 6 months post-HCT or 12 months post-HCT in patients with graft-versus-host disease requiring systemic corticosteroids. Patients were followed clinically for the development of BKPyV hemorrhagic cystitis in the first year post-HCT. Urine BKPyV PCR was checked per standard of care if patients developed symptoms of cystitis. BKPyV hemorrhagic cystitis was defined as BKPyV viruria with macroscopic hematuria and symptoms of cystitis. Risk factors for BKPyV hemorrhagic cystitis were examined using logistic regression models. RESULTS: Of 152 patients analyzed, 73 (48%) had early BKPyV viruria (33 pre-HCT and 40 post-HCT). Nine patients developed BKPyV hemorrhagic cystitis before D+40, and 7 patients after D+40. Among the 79 patients without early BKPyV viruria, none developed BKPyV hemorrhagic cystitis. The cumulative incidence of BKPyV hemorrhagic cystitis by 1-year post-HCT was 10% (95% confidence interval: 0.051-0.146). Cut point analysis demonstrated that BKPyV urine viral load ≥6.35 × 106 copies/mL was the optimal discriminator for BKPyV hemorrhagic cystitis at 1-year post-transplant (odds ratio: 7.59, 95% confidence interval: 2.27, 27.2; P = .001). CONCLUSIONS: Nearly half of HCT patients had BKPyV viruria by D+40 post-HCT. Early BKPyV viruria ≥6.35 × 106 copies/mL may help identify patients at risk for BKPyV hemorrhagic cystitis. Clinical trials of BKV therapeutics may use early BKPyV screening to identify patients at high-risk for BKPyV hemorrhagic cystitis.