Abstract
Acute graft-versus-host disease (aGvHD) continues to be a major obstacle to allogeneic haematopoietic stem cell transplantation. Thymic damage secondary to aGvHD along with corticosteroids and other non-selective T lymphocyte-suppressive agents used in the treatment of aGvHD concurrently impair thymopoiesis and negatively impact on immunoreconstitution of the adaptive immune compartment and ultimately adversely affect clinical outcome. Extracorporeal photopheresis (ECP) is an alternative therapeutic strategy that appears to act in an immunomodulatory fashion, potentially involving regulatory T lymphocytes and dendritic cells. By promoting immune tolerance and simultaneously avoiding systemic immunosuppression, ECP could reduce aGvHD and enable a reduction in other immunosuppression, allowing thymic recovery, restoration of normal T lymphopoiesis, and complete immunoreconstitution with improved clinical outcome. Although the safety and efficacy of ECP has been demonstrated, further randomised controlled studies are needed as well as elucidation of the underlying mechanisms responsible and the effect of ECP on thymic recovery.
Highlights
Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat malignant and non-malignant haematological conditions[1]
Peripheral thymic-independent expansion of surviving host T lymphocytes and/or transferred donor T lymphocytes provides a degree of immediate T lymphocyte immunity but of limited diversity and permanency[5]
Complete IR following lymphodepletion requires durable de novo thymic regeneration of naïve T lymphocytes from donor progenitor cells with a broad T cell receptor (TCR) repertoire, which requires a functioning and structurally intact thymus[8,9]
Summary
Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat malignant and non-malignant haematological conditions[1]. With selective down-regulation of immune stimulation, could reduce aGvHD and enable a reduction in other immunosuppression, facilitating thymic recovery, restoration of normal T lymphopoiesis, and complete IR (Figure 1) with improved clinical outcome as ability to fight infections improves and risk of secondary malignancy or relapse diminishes. Abbreviations aGvHD, acute graft-versus-host disease; APC, antigen-presenting cell; CDR3, complementarity determining region 3; DC, dendritic cell; ECP, extracorporeal photopheresis; HSCT, allogeneic hematopoietic stem cell transplant; IFNγ, interferon gamma; IR, immunoreconstitution; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer; STAT1, signal transducer and activator of transcription 1; TCR, T cell receptor; TEC, thymic epithelial cell; TREC, T cell receptor excision circle; Treg, regulatory T lymphocyte.
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