Association between Thymic Function and Allogeneic Hematopoietic Stem Cell Transplantation Outcome: Results of a Pediatric Study

Abstract

Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities.

<p>Optimal Delivery of Follow-Up Care After Allogeneic Hematopoietic Stem-Cell Transplant: Improving Patient Outcomes with a Multidisciplinary Approach</p>

“…Detection TCR excision circles (TRECs) in the blood are a reliable marker of thymic output [187][188][189] and may be persistently low up to 20 years after transplant. [190][191][192][193] The severity of cGvHD significantly correlates with the degree of immunosuppression and the risk of infectious complications given the damage of the lymphoid microenvironment, the adverse effects on homeostatic peripheral expansion, and the prolonged immunosuppression that hampers a robust reconstitution of the immune function of both the T and B cell compartments. Other factors that predispose to infections are age, comorbidities, and the exposure to pathogens prior to transplant.…”

Restoring T Cell Homeostasis After Allogeneic Stem Cell Transplantation; Principal Limitations and Future Challenges

“…Evaluation of thymopoiesis can be measured by T-cell receptor excision circles (TREC) that are generated from the rearrangement of the V and J segments at the TCRα locus and thus correlate with thymic output of naïve T cells ( 35 , 36 ). Depending of the robustness of the thymic output before transplantation, clinical outcomes and incidence of GVHD may vary ( 37 ). During GVHD, TREC levels are normally low and correlate with low levels of recent thymic emigrants (RTEs) detected in the blood ( 36 , 38 – 41 ).…”

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

“…They found that patients with high TREC levels have better OS, decreased incidence of severe GVHD (acute and chronic) and lower incidence of several opportunistic infections. Another study found similar results, with a correlation between high levels of sjTRECs before HSCT and a reduced risk of death mainly due to a reduction in the incidence of relapse [112]. Unfortunately, in both studies pre-transplant TREC levels were not correlated to TREC levels post HSCT or other thymic activity parameters.…”