Abstract
Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for several malignant and non-malignant hematological diseases. The clinical outcome of this procedure relies to a large extent on optimal recovery of adaptive immunity. In this regard, the thymus plays a central role as the primary site for de novo generation of functional, diverse, and immunocompetent T-lymphocytes. The thymus is exquisitely sensitive to several insults during HSCT, including conditioning drugs, corticosteroids, infections, and graft-vs.-host disease. Impaired thymic recovery has been clearly associated with increased risk of opportunistic infections and poor clinical outcomes in HSCT recipients. Therefore, better understanding of thymic function can provide valuable information for improving HSCT outcomes. Recent data have shown that, besides gender and age, a specific single-nucleotide polymorphism affects thymopoiesis and may also influence thymic output post-HSCT, suggesting that the time of precision medicine of thymic function has arrived. Here, we review the current knowledge about thymic role in HSCT and the recent work of genetic control of human thymopoiesis. We also discuss different transplant-related factors that have been associated with impaired thymic recovery and the use of T-cell receptor excision circles (TREC) to assess thymic output, including its clinical significance. Finally, we present therapeutic strategies that could boost thymic recovery post-HSCT.
Highlights
Hematopoietic stem cell transplantation (HSCT) represent the earliest form of stem cell therapy and has been used over six decades as treatment for several malignant and non-malignant blood conditions [1]
Consistent with their findings, we showed that signal joint TRECs (sjTREC) levels were not affected by acute GvHD (aGvHD) in a long-term followup study [58]
Despite other studies have not shown a significant association between T-cell receptor excision circles (TREC) and stem cell graft source [59, 68], a higher engraftment and supportive thymic function is expected in bone marrow (BM) grafts, which contain mesenchymal stromal cells and dendritic cells that can possibly engraft in the host after HSCT and support hematopoiesis
Summary
Hematopoietic stem cell transplantation (HSCT) represent the earliest form of stem cell therapy and has been used over six decades as treatment for several malignant and non-malignant blood conditions [1]. Age-related involution does not lead to a complete loss of thymic function as residual thymic output can still be retained even in advanced ages, albeit significantly reduced [46] On this matter, age is an independent risk factor related to thymic function impairment in HSCT [47], with the thymic rebound post-HSCT shown to be reduced in elderly as compared to young adults and resulting in reduced naïve T-cells production [48]. Genetic Factors Genetic background can be implicated in determining the thymic function and the rate of thymic involution In this regard, Clave et al [26] have assessed the impact of 5,699,237 common single-nucleotide polymorphisms (SNPs) on sjTREC levels in a genome-wide association study of 1,000 patients from a Milieu Intérieur cohort. Despite other studies have not shown a significant association between TREC and stem cell graft source [59, 68], a higher engraftment and supportive thymic function is expected in BM grafts, which contain mesenchymal stromal cells and dendritic cells that can possibly engraft in the host after HSCT and support hematopoiesis
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