Prognostic Impact of BK Polyomavirus Viremia Detected by Multiplex Plasma PCR Following Allogeneic Hematopoietic Cell Transplantation

Abstract

After allogeneic hematopoietic cell transplantation (allo-HCT), the reactivation of opportunistic viruses, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK human polyomavirus (BKPyV), adenovirus (ADV), and human herpesvirus-6 (HHV-6), contributes to morbidity and mortality. Moreover, concomitant reactivation of multiple viruses is not rare after allo-HCT; whether the excess mortality is driven by a particular virus or instead reflects the severity of global immune dysfunction remains unclear. To distinguish virus-specific effects from global immune dysfunction by evaluating the association between concurrently detected viremia for individual viruses and clinical outcomes after allo-HCT. We conducted a retrospective symptom-triggered correlative laboratory study using concurrent multiplex plasma PCR to test for 13 viruses. Among 432 adult allo-HCT recipients transplanted between August 2021 and December 2024, 44 symptomatic patients who underwent viral testing were included. At symptom onset, plasma samples were obtained for viral testing. Multivariable analyses used Cox proportional hazards models for overall survival (OS) and Fine-Gray proportional subdistribution hazards models for nonrelapse mortality (NRM), treating relapse as a competing risk. Risk factors for BKPyV viremia were evaluated. The median time from allo-HCT to first virus detection was 36.5 days. BKPyV and HHV-6 were most frequently detected (each 48%), whereas JC polyomavirus, CMV, EBV, and ADV were detected less frequently. In multivariable models adjusted for clinical covariates, only BKPyV viremia was independently associated with inferior OS (hazard ratio [HR] 10.27; 95% CI 3.16 to 33.31; P < .001) and higher NRM (subdistribution HR 9.40; 95% CI 2.41 to 36.68; P = .001). Causes of NRM were heterogeneous. Among patients with BKPyV viremia, no patient died directly from a BKPyV-related complication and NRM did not differ according to the presence or absence of hemorrhagic cystitis. Risk factors for BKPyV viremia included immunosuppression-related factors-prior allo-HCT, high dose total body irradiation (12 Gy), and lymphopenia (<200/µL)-as well as recipient HLA-A*24:02. In a symptom-triggered, high-risk allo-HCT population, BKPyV viremia serves as an independent prognostic marker beyond hemorrhagic cystitis and identifies patients at high risk of NRM. Prospective validation and immunologic mechanistic studies are warranted.

Keywords: BK polyomavirus; HLA-A*24:02; Multiplex plasma PCR; Nonrelapse mortality.