BK virus kinetics and associated cystitis/urethritis symptoms after PTCy-based allogeneic hematopoietic cell transplant

BK virus-associated cystitis/urethritis (BK-C) is a major cause of morbidity in allogeneic hematopoietic cell transplant (HCT) recipients. We prospectively followed weekly plasma and urine BK viral loads and associated symptoms in 169 recipients of posttransplant cyclophosphamide (PTCy)-based HCT. Patients with ≥2 positive BK specimens before day +100 were considered at-risk for developing BK-C. Many patients had detectable BK viruria already before the start of conditioning (40%) and HCT (51%), whereas baseline detectable BK viremia was less common (8% and 11%, respectively). Of 169 patients, 133 (79%) were at risk for BK-C: of these, 96 (72%) developed BK-C after a median 30 days after HCT, which lasted a median 26 days; 76 (79%) had macroscopic hematuria. BK viral levels measured in the first post-HCT month had high prognostic value for subsequent occurrence of BK-C. At time of onset, 96% and 80% had BK viruria ≥7 and ≥9 log10 IU/mL, respectively. In univariate analyses, BK-C was associated with male sex, marrow grafts, sirolimus, and myeloablative conditioning (MAC); earlier BK-C onset was associated with high-dose (compared with intermediate- or low-dose) PTCy, BK positivity at HCT, reduced-intensity conditioning (RIC), and underlying immune deficiency. Busulfan use, cyclophosphamide dosing, RIC, and underlying immune deficiency were associated with prolonged symptom duration. In recipients of MAC, PTCy dosing also correlated with symptom duration. Our study confirms a very high rate of BK-C after PTCy-based HCT; lower PTCy dose may shorten BK-C duration in specific patient subsets. Early post-HCT monitoring of BK viruria may help identify patients who will subsequently develop BK-C.