Author(s): Choi SW, Reddy P
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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.
This article was published in Nat Rev Clin Oncol
and referenced in Journal of Antivirals & Antiretrovirals