Clinical Application of Torque Teno Virus (TTV) Monitoring in Hematopoietic Stem Cell Transplant (HSCT) and Chimeric Antigen Receptor T-cell (CAR T-cell) Patients
Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. The monitoring of TTV loads can be a valuable tool in determining the risk of infection or rejection after a person undergoes a transplantation. High TTV loads may suggest a weakened immune system, while decreasing TTV loads may indicate successful immune reconstitution. Monitoring the TTV loads can provide valuable information about the overall health status of the patient post-transplant.
Aside from using TTV loads for Solid Organ Transplant (SOT) patients, Hematopoietic Stem Cell Transplant (HSCT) and Chimeric Antigen Receptor T-cell (CAR T-cell) patients may see a benefit as well. The monitoring of TTV loads after a person has a bone marrow or stem cell transplant is an essential practice, as changes in TTV loads over time can indicate the patient's immune status and response to the HSCT and/or CAR T-cell process.
Why is this crucial?
- TTV is a common virus that infects humans and can cause persistent infections. In patients with compromised immune systems, such as those undergoing HSCT and/or CAR T-cell therapy, leading to serious complications.
- Monitoring TTV loads can help healthcare providers evaluate the effectiveness of HSCT and/or CAR T-cell therapy. Studies have shown that high TTV loads in patients undergoing CAR T-cell therapy are associated with poorer treatment outcomes.
- Studies have shown that fluctuations in TTV levels may precede the onset of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) events during CAR T-cell therapy in several ways.
- Primarily, high TTV levels have been associated with an increased risk of developing CRS and ICANS in patients undergoing CAR T-cell therapy.
- Secondarily, changes in TTV levels over time can serve as an early warning sign of potential CRS or ICANS events.
- TTV infection can present with symptoms like those of CRS or ICANS, such as fever, fatigue, and neurological symptoms. By tracking TTV levels alongside clinical symptoms, healthcare providers can make more accurate diagnoses, serving as an early warning sign of potential adverse events, and aiding in the differential diagnosis.
Therefore, evaluating TTV loads after a person has a bone marrow or stem cell transplant is crucial for assessing the risk of TTV-related complications, evaluating transplant success and immune reconstitution, identifying high-risk patients, and monitoring overall health status.
In summary, the monitoring of TTV levels may provide valuable insights into the engraftment and persistence of CAR T-cell therapy in patients. Persistent high TTV levels post-treatment may suggest that the patient's immune system is unable to effectively control the TTV infection and potentially affect the engraftment and persistence of CAR T-cells. On the other hand, a decrease in TTV levels (over time) following CAR T-cell therapy may indicate successful engraftment and persistence of CAR T-cells. A reduction in TTV levels can suggest that the patient's immune system is recovering and able to control TTV infection, allowing for the effective engraftment and persistence of CAR T-cells.
Overall, monitoring TTV levels can serve as a useful biomarker for HSCT and/or CAR T-cell recipients by providing valuable information about the patient's immune status and the potential risk of infection or rejection. By closely monitoring TTV levels in conjunction with other clinical parameters, healthcare providers can better evaluate the effectiveness of HSCT and/or CAR T-cell therapies and tailor treatment strategies to optimize patient outcomes.
References:
The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.809312/full
https://bing.com/search?q=Why+do+clinicians+monitor+torque+teno+virus+levels
Torque teno virus monitoring in transplantation: The quest for standardization. DOI:https://doi.org/10.1111/ajt.15194
Understanding torque teno virus (TTV) as an immune marker. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1168400/full
Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data. https://molcellped.springeropen.com/articles/10.1186/s40348-021-00118-8
Torque Teno Virus (TTV) Biomarker Guiding Transplant Risk Management, Selection of publications, 2022 Edition. https://www.biomerieux.com/content/dam/biomerieux-com/03----our-offer/clinical/in-hospital--in-lab/products/ttv-r-gene/documents/TTV%20R-GENE%28r%29%20Selection%20Of%20Publications.pdf
Benzaquén, A., Giménez, E., Iacoboni, G. et al. Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy. Bone Marrow Transplant 59, 93–100 (2024). https://doi.org/10.1038/s41409-023-02114-0
Prioritize Patient Health with TTV Viral Load Monitoring
