Pathogenesis and Management of Graft-versus-Host Disease

Abstract

Synopsis Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic option for a variety of malignant and nonmalignant conditions. As the number of allogeneic HCT continues to increase, greater attention to improvements in supportive care, infectious prophylaxis, immunosuppressive medications and DNA-based tissue typing are continuously being made. However, graft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic HCT and limits the broader application of this important therapy. Recent advances in the understanding of the pathogenesis of GVHD have led to new approaches to its management, including utilizing its role in preserving the graft versus leukemia effect following allogeneic transplant. Here we review the important elements in the complex immunological interactions involving cytokine networks, chemokine gradients and the direct mediators of cellular cytotoxicity that cause clinical GVHD, and discuss the risk factors and strategies for management of GVHD.

Effector CD4+ T cells, the cytokines they generate, and GVHD: something old and something new

“…Subsequent work indicated that donor T cells that recognize minor or major histocompatibility differences in the host were critical mediators of GVHD. [2][3][4] Thus, a role for donor T cells in the pathogenesis of GVHD has been clear for Ͼ 30 years. However, the mechanism by which T cells mediate this process is not completely understood.…”

Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study

“…6 Whereas the degree of HLA mismatching exerts the strongest genetic effect on risks, such as acute and chronic GVHD, relapse, and survival, non-HLA polymorphisms in immune response genes, such as cytokines, at least modify these risks, as shown in studies that have shown light on the pathobiology of HSCT, 7,8 and the relation of cytokine gene polymorphisms, 6,9,10 with gene expression and biologic effects. [11][12][13][14][15] Non-HLA gene polymorphisms have been widely studied (a systematic search conducted revealed 192 studies over the last 2 decades).…”

Dendritic Cells in Hematopoietic Stem Cell Transplantation

“…The 1966 Billingham criteria clearly accounted for the presence of viable and immunologically functional effector cells as a prerequisite for the development of GVHD (Billingham, 1966). More recent models of GVHD (Choi et al, 2010;Ferrara & Reddy, 2006;Goker et al, 2001;Li et al, 2009a) also take into account the key role of antigen presentation in its development by stating that activation of APC precedes activation and clonal expansion of T cells in the immune cascade. Host APC play a crucial role in the graft-versus-host reaction by presenting mismatched recipient antigens to donor T cells (Goker et al, 2001).…”