T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

Gaballa, Ahmed; Sundin, Mikael; Stikvoort, Arwen; Abumaree, Muhamed; Uzunel, Mehmet; Sairafi, Darius; Uhlin, Michael

doi:10.3390/ijms17101705

Cited by 28 publications

(20 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous reports have shown that assessing recipient thymic and bone marrow function can predict HSCT outcome [4,5]. A practical method for monitoring thymopoiesis and B cell reconstitution after transplantation is the quantification of T cell receptor excision circles (TRECs) generated during T cell receptor gene rearrangement and kappa-deleting recombination excision circles (KRECs) generated during Ig light chain rearrangement, respectively [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Törlén

Gaballa

Remberger

et al. 2019

Biology of Blood and Marrow Transplantation

Self Cite

View full text Add to dashboard Cite

A B S T R A C T Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning regimen and post-transplantation immunosuppression are risk factors for prolonged immunodeficiency. Nevertheless, the effects of different immunosuppressive protocols on lymphocyte output and replicative capacity have not been investigated. Here we assessed T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate versus tacrolimus/sirolimus; n = 200).Results showed that medians of TREC, KREC, and TL were not significantly different between the prophylaxis groups at any assessment time point during follow-up (24 months), but the kinetics of TREC, KREC, and TL were significantly influenced by other transplantation-related factors. Older recipient age, the use of antithymocyte globulin before graft infusion, and use of peripheral blood stem cell grafts were associated with lower TREC levels, whereas acute GVHD transiently affected KREC levels. Patients with lymphocyte excision circle levels above the median at 6 months post-transplantation had reduced transplantation-related mortality and superior 5-year overall survival (P < .05). We noticed significant T cell telomere shortening in the patient population as a whole during follow-up. Our results suggest that lymphocyte reconstitution after transplantation is not altered by different immunosuppressive protocols. This study has been registered at ClinicalTrials.gov (identifier: NCT00993343).

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Törlén

Gaballa

Remberger

et al. 2019

Biology of Blood and Marrow Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many clinical situations associated with aging have been described as possible causes of impaired thymic function, including changes in growth factor and cytokine expression, low hormone production, and bone marrow loss ( 7 , 8 ). TREC quantification has been shown in various studies to be more reliable for evaluation of thymic function ( 9 – 16 ). A series of observations on TREC dynamics during human immunodeficiency virus (HIV) infection and treatment and in autologous and allogeneic hematopoietic stem cell transplantation (HSCT) confirmed the usefulness of TREC analysis as a quantitative marker for thymic function.…”

Section: Introductionmentioning

confidence: 99%

Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation

et al. 2018

View full text Add to dashboard Cite

Hematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/μg DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26–31.53; p < 0.001]. Our results showed that a group of older individuals (≥50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80–36.20) for low sjTREC values compared with younger individuals (≤24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (≥50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (≥50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.

show abstract

“…Several factors injuring the thymus can delay the recovery of thymopoiesis after HSCT including: increasing age of the recipient, occurrence and grade of acute or chronic graft versus host disease (aGvHD, cGvHD), intensity of conditioning, source of stem cells, infections in the transplant period (especially CMV reactivation) or previous treatment of the underlying disease (malignant or non-malignant) [15,17]. Median age of the patients at the time of HSCT was 7.7 years (range 6 months to 19.5 years).…”

Section: Introductionmentioning

confidence: 99%

Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children

Janeczko-Czarnecka¹,

Rybka²,

Ryczan‐Krawczyk³

et al. 2020

cejoi

View full text Add to dashboard Cite

thymic output was studied prospectively in 52 children who underwent allogeneic hematopoietic stem cell transplantation (allo-Hsct). thymic activity was assessed by quantification of recent thymic emigrants (rte) discriminated from the rest of naive t cells by immunophenotype cD3+/cD4+/ cD31+/cD45ra+. thymic output was analyzed in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence thymopoiesis: underlying disease, type of Hsct, source of stem cells, age of recipient and donor, type of conditioning, implemented graft versus host disease (gvHD) prophylaxis, viral reactivations (herpes viruses cytomegalovirus-cMV, epstein-Barr virus-eBV, adenovirus-aDV, Bk virus-BkV), occurrence and grade of both acute and chronic graft versus host disease (agvHD, cgvHD) and number of transplanted cD34 cells/kg. the absolute count of rte in peripheral blood was evaluated at 6 time points: before the conditioning and on days +15, +30, +60 , +90 and +180 after Hsct. occurrence of grade ii-iV agvHD was the most important factor associated with low rte counts after Hsct. History of malignant disease, and transplantation from matched unrelated donor were risk factors for lower thymic output. we found a weak inverse correlation between the age of the recipient and thymic output on post-Hsct day +180. source of stem cells, type of conditioning, viral reactivations, occurrence of chronic gvHD, age of the donor and the number of transplanted cD34 cells/kg did not affect thymopoiesis in our study group. these preliminary findings and identification of risk factors for deterioration of thymic activity may in the future help in selecting candidates for thymus rejuvenation strategies.

show abstract

T Cell Receptor Excision Circle (TREC) Monitoring after Allogeneic Stem Cell Transplantation; a Predictive Marker for Complications and Clinical Outcome

Cited by 28 publications

References 107 publications

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation

Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children

Contact Info

Product

Resources

About