Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associated variants in Crohn’s disease, have recently been suggested as important candidate gene markers in the outcome of HSCT. It was originally postulated that as the clinical manifestation of inflammatory responses characteristic of several post-transplant complications was of notable similarity to those seen in Crohn’s disease, it was possible that they shared a common cause. Since the publication of this first paper, numerous studies have attempted to replicate the results in different transplant settings. The data has varied considerably between studies, and as yet no consensus on the impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the existing literature, summarise current theories as to why the data differs, and suggest possible mechanisms by which the SNPs affect HSCT outcome. 1. Introduction Allogeneic haematopoietic stem cell transplantation (HSCT) is an important treatment option in the management of many diseases including malignant and non-malignant haematological disorders, immune deficiencies and inborn errors [1]. The increased knowledge of transplant biology and the effects of clinical factors and HLA matching have improved outcome. The primary choice of donor is usually an HLA-matched sibling, but the probability of a sibling being HLA identical is only 25%, a problem that is exacerbated due to small family sizes that are usually found today. Alternative allogeneic donor sources are thus often required and have now become an important and viable option. There are currently over 19.8 million volunteer unrelated donors (UDs) that have been recruited to registries around the world, with an additional 543,000 umbilical cord blood units also being available (as of September 2012) (http://www.bmdw.org/). The improvement in transplant techniques and practice has resulted in similar survival prospects for recipients of a well-matched UD as that using a sibling [2, 3]. However, the risk of posttransplant complications such as graft-versus-host disease (GvHD) and delayed immune reconstitution leading to infection is increased [4].
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