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

By inergency On Mar 17, 2024

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Maggi et al. (2010) [34] Four patients with acute leukemia Before total body irradiation (TBI) and after allo-SCT (within the first 30 days; in 2 patients at days +50, +80, and +110 after transplantation)

All patients (n = 4) developed plasma TTV DNAemia before TBI and 3 after allo-SCT (day +30)
TTV DNA load before TBI, median, 5.15 log₁₀ copies/mL and median, 5.4 log₁₀ copies/mL at day +80.
Starting from day +26, TTV DNAemia consistently increased in parallel with white blood cells in peripheral blood.

Masouridi-Levrat et al. (2016) [26] A total of 121 patients. AML (58), ALL (15), MDS (12), NHL (10), MPS (6), MM (9), HL (5), CML (3), CLL (1), and MDPS (1) At baseline (days +4.3 ± 5.4 post-transplant) and at 1 and 3 months afterward.

At baseline, 85 out of 121 patients had detectable TTV DNAemia, and all patients (77 out of 77) who were still available for follow-up had detectable TTV DNA at the end of it.
At baseline, TTV DNA load was 2.38 log₁₀ copies/mL (median) and 5.47 log₁₀ copies/mL (median) 3 months later.
TTV DNA load after transplantation was higher in patients who received immune suppression, including prednisone.
At baseline, TTV DNA load was higher in patients with ALL or NHL

Albert, et al. (2017) [27] A total of 72 patients. HL (5), NHL (15), ALL (7), CLL (6), AML (19), CML (1), MM (5), MDS (10), and others (4) Before conditioning,
and at days +20, +30, +60,
and +90 after allo-SCT.

Before conditioning 44/55 had detectable DNA load. A total of 23/23 patients with paired samples between days +20 and +90 had detectable TTV DNA in all available samples.
TTV DNA load reached peak levels at around day +90 (median, 5.0 log₁₀ copies/mL)
TTV DNA load in plasma decreased dramatically after conditioning, in parallel with absolute lymphocyte counts.
TTV DNA load increased steadily after engraftment, in parallel with absolute lymphocyte counts (rho = 0.21; p = 0.09)

Wohlfarth et al. (2018) [28] A total of 50 patients. ALM (25); ALL (9) MDS (6), NHL (3), and others (7) Before conditioning, at the time of allo-SCT and days +10, +30, +50, +80, +120, +160, +200,+ 250, +300, and +365 after allo-SCT

A total of 40/50 patients (80%) had detectable TTV DNA loads before conditioning and all developed plasma TTV DNAemia during the follow-up period
TTV DNA load peaked (8.32 log₁₀ copies/mL) at around day +80
TTV DNA levels showed a weak yet significant inverse correlation with absolute lymphocyte counts following engraftment (rho = −0.27; p < 0.01)
TTV DNA load reached a stable plateau towards the end of the follow-up period.

Albert et al. (2018) [35] A total of 38 patients. NHL (14), HL (1), AML (4), CLL (3), AML (6), MM (2), MDPS (6), and others (2) Before the initiation of conditioning (day −7) and days +30, +50, +90 after allo-SSCT.

At baseline (pre-transplant), TTV DNA was detected in all saliva samples (23/23) and all but 3 plasma samples (20/23)
At day +90, all saliva samples (25/25) and all but one plasma specimen (24/25) had detectable TTV DNA.
The kinetics of TTV DNA load in saliva and plasma specimens were comparable. The TTV DNA load peak was reached at day +90 in both compartments (median, 6.1 log₁₀ copies/mL in saliva and 4.7 log₁₀ copies/mL in plasma).
A direct correlation between absolute lymphocyte counts and TTV DNA loads in plasma was seen after engraftment. (rho = 0.507; p < 0.0001)

Albert et al. (2019) [36] A total of 33 patients: Lymphoma (12), leukemia (12), MM (4), MDS (3), and myelofibrosis (2) Before conditioning and at days +20, +30, +40, +50, +60, +90, +120, +180, +210 after allo-SCT

Detection rate over the study period 100% (33/33).
Increasing TTV DNA levels after engraftment peaking at + 90 (median, 5.1 log₁₀ copies/mL)
TTV DNA loads measured within days +120 and +210 correlated inversely with absolute lymphocyte counts (rho = −0.26; p = 0.003)

Mouton et al. (2020) [32] A total of 41 patients. Myeloid neoplasm and acute leukemia (37), Mature lymphoid/histiocytic, and dendritic neoplasms (4) Patients were enrolled a median of 6 months (IQR, 5–8) post transplant.

DNA TTV was detected in 100% (41/41) of patients.
Peak TTV DNA load was 3.9 log₁₀ copies/mL.
There was no significant correlation between TTV DNA load and absolute lymphocyte counts or CD3⁺ T-cells.
TTV DNA load was inversely correlated with CD3⁺ T-cell proliferation capacity (%) (rho = −0.39, p = 0.01)

Schmitz et al. (2020) [29] A total of 123 patients. AML (58), ALL (9), MDS (33), NHL (11), and others (12) A total of 18 different time points were examined from before allo-HSCT to 345 days post.

A total of 62/123 (50.4%) had measurable TTV DNA before transplantation.
Peak TTV DNA was reached at day +90 (median, 5 log₁₀ copies/mL).
No statistically significant correlation was found between TTV DNA load and any lymphocyte subset.
Patients with lymphatic malignancies had significantly more often detectable TTV DNA before allo-SCT compared with patients with myeloid diseases.

Pradier et al. (2020) [37] A total of 168 patients. AML (78), ALL (17), MDS (22), MPS (11), Lymphoma (12), MM (11), and others (17). Peripheral blood samples were collected at days 0, +50, +100, +150, +200, +300, +400, +547, and 2 to 9 years post-allo-SCT.

TTV titer reached a peak value at day +100 (median 6.4 log₁₀ copies/mL, IQR 5.1–7.7)
At day 100, there was an inverse correlation between TTV levels and lymphocyte counts, particularly with CD4⁺ T-cells and NK cells. The correlation between TTV and CD4⁺ T-cell counts persisted until day 300. No significant correlation with any cell subset was observed before day 100 or after day 400.

Spiertz et al. (2023) [30] A total of 59 patients. AML (31) ALL (6), CML (2), CLL (4), MDS (10), and others (6) Upon infusion of hematopoietic cells (between day −7 and +10), and at days +14, +21, +28, +56, +90, +365 after allo-SCT

The prevalence of TTV DNA detection at baseline was 77% 42(54).
All patients tested positive for TTV DNA on day +90. Furthermore, 95.6% of the samples remained TTV DNA positive one year after allo-SCT
TTV DNA load peak was reached at day +56 (7.08 log₁₀ copies/mL)

Forque et al. (2023) [38] A total of 75 patients. AML (28), H (13) NHL (15) MDS (4) MF (4), CML (3), CLL (3), and others (5) Before conditioning, at baseline, and after allo-SCT (+30, +60, +90, +120, and +180)

A total of 73/75 patients had detectable TTV DNA load (97%) over the study period.
The TTV DNA load decreased by day +30 compared with that at baseline (a reduction of 15%), and then increased, reaching its peak by day +90 with a median load of 7.29 log₁₀ copies/mL.

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