The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Julia Schmitz; Guido Kobbe; Mustafa Kondakci; Esther Schuler; Max Magorsch; Ortwin Adams

doi:10.1016/j.bbmt.2019.11.002

The Value of Torque Teno Virus (TTV) as a Marker for the Degree of Immunosuppression in Adult Patients after Hematopoietic Stem Cell Transplantation (HSCT)

Biol Blood Marrow Transplant. 2020 Apr;26(4):643-650. doi: 10.1016/j.bbmt.2019.11.002. Epub 2019 Nov 9.

Authors

Julia Schmitz¹, Guido Kobbe², Mustafa Kondakci², Esther Schuler², Max Magorsch³, Ortwin Adams⁴

Affiliations

¹ Institute for Virology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany.
² Department of Haematology, Oncology and Clinical Immunology, University Hospital of Duesseldorf, Duesseldorf, Germany.
³ Technical University of Dortmund, Dortmund, Germany.
⁴ Institute for Virology, Medical Faculty, University of Duesseldorf, Duesseldorf, Germany. Electronic address: ortwin.adams@uni-duesseldorf.de.

PMID: 31712192
DOI: 10.1016/j.bbmt.2019.11.002

Abstract

Torque teno virus (TTV) is a nonenveloped, single-stranded, circular DNA virus of the family of Anelloviridae. The first contact with TTV usually occurs in early childhood, followed by persistent infection in bone marrow and lymphocytes. Increased levels of TTV-DNA are found in the serum in various states of immune deficiency. The objective of this study was to assess if monitoring of TTV viremia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a predictive marker for immune-related clinical complications. In a retrospective study, 2054 whole-blood samples from 123 patients were tested for viral loads of TTV-DNA by real-time PCR within 345 days after allo-HSCT. We enrolled all patients who underwent allo-HSCT between September 2015 and April 2018. Clinical and laboratory data were collected and statistically analyzed. Patients with an underlying lymphatic malignancy had significantly higher torque teno (TT) viral loads compared with patients with an underlying malignant myeloid disease (P < .05). Complete remission before allo-HSCT correlated significantly with higher TT viral loads after allo-HSCT (P < .05). Myeloablative conditioning regimens led to significantly higher TT viral loads than reduced-intensity conditioning regimens (P < .05). A higher anti-thymocyte globulin (ATG) dose was associated with a significantly higher TT viral load. We did not observe any significant differences of TT viral load correlating with accompanying clinically relevant events such as virus reactivations (cytomegalovirus, Epstein-Barr virus, Adenovirus), acute graft-versus-host disease (aGVHD), relapse, or death. TT viral load after allo-HSCT did weakly correlate with T cell, T suppressor cell, T helper cell, and natural killer and B cell count. Although statistically significant differences between study groups were observed, virus reactivations, aGVHD, and clinical outcomes could not be predicted by monitoring TTV viremia. Therefore, TTV seems not to be suitable as a marker for the degree of immunosuppression or as a prognostic marker for clinically critical events in patients after allo-HSCT.

Keywords: Hematopoietic stem cell transplantation (HSCT); Prognostic biomarker; Torque Teno virus (TTV).

MeSH terms

Adult
Child, Preschool
DNA Virus Infections*
Epstein-Barr Virus Infections*
Hematopoietic Stem Cell Transplantation*
Herpesvirus 4, Human
Humans
Retrospective Studies
Torque teno virus*
Viral Load