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

Nature Reviews Clinical Oncology volume 11, pages 536–547 (2014)Cite this article

Subjects

Key Points

  • Acute graft-versus-host disease (GVHD) remains a significant barrier to the wider application of allogeneic haematopoietic stem cell transplantation (HSCT)

  • Clinically significant acute GVHD develops in approximately 40–60% of patients undergoing allogeneic HSCT

  • The most widely used approach to prevent life-threatening acute GVHD is prophylaxis with a calcineurin inhibitor-based regimen typically administered during the first 180 days of HSCT

  • Based on improved biological insights of the pathophysiology of GVHD, newer approaches that target T cells and B cells of the immune system are being tested in clinical trials

  • New agents targeting multiple pathways coupled with a better understanding of the molecular interactions mediating GVHD are required to develop effective strategies to prevent this complication and avoid adverse effects

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.

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Figure 1: Standard and emerging therapies for the prevention of acute GVHD.
Figure 2: Effects of HDAC inhibition in the prevention of acute GVHD.

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  1. Blood and Marrow Transplantation Program, University of Michigan, 1500 East Medical Center Drive, 3312 Cancer Center, Ann Arbor, 48109-5942, MI, USA

    Sung Won Choi & Pavan Reddy

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  1. Sung Won Choi
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  2. Pavan Reddy
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S.W.C. and P.R. researched data for article, reviewed and edited the manuscript before submission, substantially contributed to discussion of content and wrote the manuscript.

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Correspondence to Sung Won Choi.

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The authors declare no competing financial interests.

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Supplementary Table 1

Clinical trials (active, recruiting) investigating GVHD prevention strategies† (DOCX 57 kb)

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Choi, S., Reddy, P. Current and emerging strategies for the prevention of graft-versus-host disease. Nat Rev Clin Oncol 11, 536–547 (2014). https://doi.org/10.1038/nrclinonc.2014.102

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