title: Clinical strategies to enhance thymic recovery after allogeneic hematopoietic stem cell transplantation.
abstract: The thymus is particularly sensitive to injury caused by cytoreductive chemo- or radiation therapy, shock, infection and graft versus host disease. Insufficient thymic recovery has been directly correlated with increased risk of opportunistic infections and poor clinical outcomes in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Prolonged immune deficiency is particularly pronounced in older patients whose thymi are already significantly impaired due to age-related thymic involution. Preclinical and clinical studies have revealed several strategies that can enhance thymic function and immune reconstitution after transplant, including sex steroid ablation, growth factors (growth hormone, keratinocyte growth factor, insulin-like growth factor 1, interleukin-7) and ex vivo generated precursor T cells. In addition, recent studies have shown that other approaches, such as interleukein-22 and nutritional changes, may represent additional candidates to enhance thymic regeneration. In this review we provide updates on these strategies and comment on their potential to be translated into clinical therapies.
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States; Department of Clinical and Experimental Medicine, University of Perugia, 06122 Perugia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Velardi
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D056747:Immunomodulation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D012038:Regeneration; D013950:Thymus Gland / Q000502:physiology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D000097043:Interleukin-22
chemical_list: D012739:Gonadal Steroid Hormones; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D000097043:Interleukin-22
keywords: Allogeneic hematopoietic stem cell transplantation; Immune regeneration; Thymus