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.

Torque Teno Virus DNA Load in Blood as an Immune Status Biomarker in Adult Hematological Patients: The State of the Art and Future Prospects

“…Some studies assessed the potential value of TTV DNA load as a biomarker anticipating the occurrence of certain viral infection events [ 30 , 33 , 38 , 42 ]. Albert et al [ 42 ] investigated whether the early kinetics of plasma TTV DNAemia after allo-SCT were associated with the subsequent occurrence of Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) DNAemia.…”

“…Supporting these findings, Spiertz et al [ 30 ] observed that a TTV DNA load below 3 log 10 copies/mL measured between Day −7 and +10 was significantly associated with a higher risk of developing CMV DNAemia. In turn, Forqué et al [ 38 ] established TTV DNA load cut-offs (≥4.40 log 10 -pretransplant—and ≥4.58 log 10 -baseline—copies/mL) that predicted the occurrence of Polyomavirus BK hemorrhagic cystitis (BKPyV-HC) with a sensitivity of ≥89% and a negative predictive value of ≥96%. In turn, Gilles et.…”

“…Pradier et al [ 37 ] showed that patients with high TTV DNA loads at day +100 (>6.7 log 10 copies/mL) tended toward a higher cumulative incidence of grades II-IV aGvHD at six months post transplant. Forqué et al [ 38 ] found that TTV DNA loads > 3.38 log 10 copies/mL at day +30 had a 90% sensitivity and 97% negative predictive value for anticipating aGvHD, whereas TTV DNA loads > 5.07 log 10 predicted the occurrence of grades II-IV aGvHD with high sensitivity (83%), specificity (91%), and negative predictive value (98%).…”