Kinetics of Torque Teno virus DNA in stools may predict occurrence of acute intestinal graft versus host disease early after allogeneic hematopoietic stem cell transplantation

Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft-versus-host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft-versus-host disease (aIGvHD). In this prospective two-center study we recruited a total of 83 non-consecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantitated in paired stool samples collected at a median of 2 days prior to cell infusion and at a median of 14 days after allo-HSCT by real-time PCR. Thirty-seven patients developed aGVHD, of whom 25 had aIGVHD (diagnosed at a median of 42 days after allo-HSCT). Median TTV DNA load values in post-transplant stools specimens were comparable (P=0.34) in patients with or without subsequent aIGvHD; nevertheless, a falling trajectory (decrease in TTV DNA load >0.5 log10 copies/0.1 g) in paired pre-transplant and pos-transplant specimens was independently associated with the occurrence of aIGvHD (OR, 5.2; 95% CI, 1.3-21.3; P = 0.02). Notably, displaying a rising trajectory had a negative predictive value of 87.5% for aIGvHD. In summary, in this hypothesis-generating study we suggest that the decrease in TTV DNA load from baseline in stool specimens may identify patients at risk of aIGVHD.