Current and emerging strategies for the prevention of graft-versus-host disease

Nat Rev Clin Oncol. 2014 Sep;11(9):536-47. doi: 10.1038/nrclinonc.2014.102. Epub 2014 Jun 24.

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Calcineurin Inhibitors
  • Cytokines / antagonists & inhibitors
  • DNA Methylation
  • Genes, Transgenic, Suicide
  • Genetic Therapy
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Mesenchymal Stem Cells
  • Molecular Targeted Therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation, Homologous / adverse effects

Substances

  • Antineoplastic Agents
  • Calcineurin Inhibitors
  • Cytokines
  • Histone Deacetylase Inhibitors
  • Immunosuppressive Agents