title: Current and emerging strategies for the prevention of graft-versus-host disease.
abstract: Graft-versus-host disease (GVHD) represents the most serious and challenging complication of allogeneic haematopoietic stem-cell transplantation (HSCT). New insights on the role of regulatory T-cells, T cells, and antigen-presenting cells have led to an improved understanding of the pathophysiology of GVHD. However, little progress has been made since the introduction of calcineurin-inhibitor-based regimens in the mid-1980s. Despite standard prophylaxis with these regimens, GVHD still develops in approximately 40-60% of recipients. Thus, there is a need for developing newer approaches to mitigate GVHD, which may facilitate the use of allogeneic HSCT for the treatment of a wider range of haematological cancers. We discuss the rationale, clinical evidence, and outcomes of current (and widely employed) strategies for GVHD prophylaxis, namely calcineurin-inhibitor-based regimens (such as cyclosporine or tacrolimus) combined with methotrexate or mycophenolate mofetil. We assess the clinical evidence for emerging approaches in the prevention of GVHD, including therapies targeting T cells or B cells, the use of mesenchymal stem cells, chemo-cytokine antagonists (such as maraviroc, TNF-α inhibitor, IL-2 receptor antagonist, IL-6 inhibitor), and the use of novel molecular regulators that target multiple cell types simultaneously, including atorvastatin, bortezomib, and epigenetic modulators.
authors: Blood and Marrow Transplantation Program, University of Michigan, 1500 East Medical Center Drive, 3312 Cancer Center, Ann Arbor, MI 48109-5942, USA.
authors: Sung Won
authors: SW
authors: Choi
authors: Blood and Marrow Transplantation Program, University of Michigan, 1500 East Medical Center Drive, 3312 Cancer Center, Ann Arbor, MI 48109-5942, USA.
authors: Pavan
authors: P
authors: Reddy
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D065095:Calcineurin Inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D019175:DNA Methylation; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D059630:Mesenchymal Stem Cells; D058990:Molecular Targeted Therapy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D065095:Calcineurin Inhibitors; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents