Dynamics of Torque Teno virus viremia could predict risk of complications after allogeneic hematopoietic stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for several hematological diseases. However, the first year post-transplantation is often complicated by infections and graft-versus-host disease (GVHD). Improvements in immunological monitoring could reduce such post-transplant complications. Torque Teno virus (TTV), a chronically persisting DNA virus, is reported to be a marker for immune function in immunocompromised patients. In the present study, the TTV kinetics were analyzed to investigate the potential role of TTV viremia as immune-competence read-out after allo-HSCT. Twenty-three monocentric allo-HSCT recipients were retrospectively tested for TTV-DNA in whole blood at given day post-transplant. Dynamics of TTV viremia was analyzed with respect to episodes of non-TTV viral reactivations (CMV, EBV, and BKPyV), acute GVHD, and recovery of immune cells. Recipients affected by persisting viral infections and/or GVHD during the first 100 days after allo-HSCT showed a significantly higher median TTV load at day +30 than patients with a less complicated clinical course (p = 0.005). This was also associated with a total lymphocyte count <5.5E+08 cells/L in this high-risk group (p = 0.039). These findings suggest that TTV could represent an additional parameter to identify patients at higher risk for complications in the first 100 days following allo-HSCT. Prospective studies, including the monitoring of lymphocyte subsets, are required to define the potential use of TTV in immunological monitoring after allo-HSCT.

The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients

“…In the absence of data on EBV-specific T-cell immunity, we speculate that the time span for TTV DNA load measurements (the longest period between days 20 and 50) may have been insufficient to gauge the level of EBV-specific T-cell reconstitution, which often occurs at later stages after allo-HSCT. 33,34 Our data differ from those of Gilles et al 35 who found significantly higher TTV DNA loads at day +30 after transplantation in patients with CMV or EBV reactivation and/or aGvHD, thus supporting the idea that TTV DNA load may behave as a surrogate marker for immunosuppression. In our series, TTV DNA loads quantified prior to transplant as well as those those measured at days 20 and 30 after transplantation were comparable in patients with or without subsequent CMV DNAemia (either requiring preemptive antiviral therapy or not), although a trend towards lower TTV DNA load levels by days 20 and 30 after transplantation was observed in the former patients.…”

“…Perhaps more importantly, there are substantial differences in the clinical characteristics of the patients included in each of the comparison groups: in Gilles et al 35 all the patients with CMV or EBV reactivation appeared to have developed aGvHD, a condition which leads to a significant increase in TTV DNA load, 12,13 whereas in our study patients with or without CMV or EBV DNAemia (treated or untreated) were balanced in terms of the incidence of aGvHD.…”

Torquetenovirus Dynamics and Immune Marker Properties in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Longitudinal Study

“…Biomarkers for GVHD and markers of functional immune competence are desperately needed in HSCT recipients, because the delicate adjustments of immunosuppressive therapy required in these patients are still widely guided by clinical intuition and experience rather than by objective parameters [7]. Furthermore, complications such as infections and relapse of the underlying disease are strongly connected to the immunogenic capabilities of the immune system following donor engraftment and may be represented by the TTV burden in the host [8]. Motivated by these considerations, in this study we analyzed the dynamics of TTV plasma loads in a prospective cohort of HSCT recipients and investigated possible associations with frequent immune-related complications in this group (ie, GVHD, infection, disease relapse, and cytomegalovirus [CMV] and Epstein-Barr virus [EBV] reactivation).…”

Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation

“…Moreover, the area under a curve of plasma TTV DNA loads between days +20 and +30 after allo‐HSCT allows the estimation of the risk of high‐level cytomegalovirus DNAemia . Nevertheless, the available data also suggest that once the TTV DNA load reaches a plateau, its magnitude may reflect the net state of immunosuppression, as rising plasma TTV DNA levels are seen in episodes of severe acute graft‐versus‐host disease requiring corticosteroid therapy at high doses …”

“…7 Nevertheless, the available data also suggest that once the TTV DNA load reaches a plateau, its magnitude may reflect the net state of immunosuppression, as rising plasma TTV DNA levels are seen in episodes of severe acute graft-versus-host disease requiring corticosteroid therapy at high doses. 5,6,8,9 Although T lymphocytes appear to be the main target for TTV replication, 10,11 other cell types of nonhematopoietic origin may also be fully permissive, thus potentially contributing to the TTV burden. 1,2 Pertinent to this study, TTV DNA is frequently detected in saliva from TTV-infected healthy individuals.…”