Evaluating Thymic Function After Human Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era
Ahmed Gaballa, Emmanuel Clave, Michael Uhlin, Antoine Toubert, Lucas C. M. Arruda
Abstract
Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for several malignant and non-malignant hematological diseases. Nonetheless, 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. Thymus is exquisitely sensitive to several insults during HSCT, including conditioning drugs, corticosteroids, infections and graft-versus-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 role and personalized thymic function can provide a valuable avenue for improving HSCT outcomes. Recent data have been showing that beside sex and age, a specific single-nucleotide polymorphism affect 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 works 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.