Monitoring of plasma Torque teno virus, total Anelloviridae and Human Pegivirus 1 viral load for the prediction of infectious events and acute graft versus host disease in the allogeneic hematopoietic stem cell transplantation setting

Abstract

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log₁₀ (pretransplant) and ≥4.58 log₁₀ (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log₁₀ by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD.

Keywords: BK-virus cystitis; Cytomegalovirus DNAemia; Human Pegivirus; TTV; aGvHD; infection; total Anelloviridae; viral load.