Incidence and Nature of BK and Adenovirus Infections in Post-Transplant Cyclophosphamide-Based Adult Allogeneic Hematopoietic Cell Transplant

Introduction Post-transplantation cyclophosphamide (PTCy) has been widely adopted to reduce graft-vs-host disease (GvHD) sufficiently to permit HLA haplotype disparate allogeneic hematopoietic cell transplantation (HCT). PTCy has been associated with increased risk of viral infections. Our objectives were to evaluate the frequency & severity of viremia and hemorrhagic cystitis (HC) due to adenovirus (ADV) and BK polyoma virus (BKV) and the associated mortality by day 180 post-HCT (D180) in a large single institution cohort of adult patients (pts) who received PTCy. Methods This is a retrospective review of consecutive adult HCT with PTCy-based regimen. Routine weekly monitoring for ADV with quantitative PCR in plasma was performed from D14 through D100, and as clinically indicated through D180. Evaluation of BKV and ADV in urine were symptom based. Pts with BKV viruria were also tested for BKV in plasma. ADV and BKV viremia was defined by ≥1 viral load (VL) >1,000 copies/mL by D180. HC was defined as HC grade 2-4 by the Bedi scale. Because the magnitude and duration of ADV and BKV VL in the plasma are used as predictors of outcomes and to guide treatment decisions, we further stratified patients by ≥2 consecutive VL >1,000 and or by ≥1 VL >10,000 copies/ml. Results From 2016-2022, 290 pts received 293 HCT. Baseline characteristics are in Table 1.Overall, 61 (21%) unique HCT had at least 1 viral infection. By D180, 14 (4.8%) pts had ADV viremia, 35 (11.9%) had BKV viremia; and 32 (10.9%) had HC (grade 2-4). Eight (2.7%) and 16 (5.5%) pts had ≥ 2 consecutive ADV and BKV VL >10,000 copies/mL respectively (Table 2). Of 6 pts with ADV VL >10,000 copies/ml, 2 had ADV-HC (grade 2 & 4). Of the 6 pts, 4 pts with concomitant GvHD received cidofovir along with tapering of corticosteroids with virologic response, one pt received brincidofovir primarily for CMV infection, 2 pts were not treated (due to spontaneous resolution and death due to progression of disease in 1 patient each).In the 35 pts with BKV viremia (11.9%), the median viral load was 7300 copies/mL (IQR 1850-15550). The median time to BK viremia was 57 days (range 38-86).Of the 32 pts (10.9%) who developed grade ≥2 HC (Table 3), 27 (9.2%) had BKV-HC and 5 (1.7%) had ADV-HC (+/-BKV). Grades 3-4 HC were seen in 12 patients (4.1%). No deaths were primarily related to ADV or BKV infections. Conclusion By D180, 4.7% and 11.9% of PTCy-based HCT developed ADV and BKV viremias respectively. Half or more of them were low grade ≤10,000 copies/mL and not associated with end organ disease. High grade and protracted ADV viremia were seen in patients with active GvHD on corticosteroids. While the incidence of grade 3-4 HC was 4%, further studies are needed to evaluate associations with renal injury and other long term clinical outcomes. There are currently no approved therapies for these infections. Novel antiviral prevention and treatment strategies for BKV and ADV infections are needed.