Graft-versus-host disease
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Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient. Graft-versus-host disease can occur even when HLA-identical sibling are the donors. HLA-identical siblings or HLA-identical unrelated donors (called a minor mismatch as opposed to differences in the HLA antigens, which constitute a major mismatch) often still have genetically different proteins that can be presented on the MHC.
While donor T-cells are undesirable as effector cells of graft-versus-host-disease, they are valuable for engraftment by preventing the recipient's residual immune system from rejecting the bone marrow graft (host-versus-graft). Additionally, as bone marrow transplantation is frequently used to cure malignant disorders (most prominently the leukemias), donor T-cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host-disease aspects of T-cell physiology from the desirable graft-versus-tumor effect.
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Types
Clinically, graft-versus-host-disease is divided into acute and chronic forms. Acute is defined as the fulminant form of the disease observed within the first 100 days post-transplant. The chronic form of graft-versus-host-disease is defined as that which occurs after 100 days. The distinction is not arbitrary: acute and chronic graft-versus-host-disease appear to involve different immune cell subsets, different cytokine profiles, and different types of target organ damage.
Classically, graft-versus-host-disease is characterized by selectively damaging the liver, skin and mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs include the immune system (the hematopoietic system) itself and the lungs in the form of idiopathic pneumonitis. Chronic graft-versus-host-disease damages the above organs, but also causes changes to the connective tissue (e.g. of the skin)
Prevention
Graft-versus-host-disease can largely be avoided by performing a T-cell depleted bone marrow transplant. These types of transplants result in reduced target organ damage and generally less graft-versus-host-disease, but at a cost of diminished graft-versus-tumor effect, a greater risk of engraftment failure, and general immunodeficiency, resulting in a patient more susceptible to viral, bacterial, and fungal infection. In a single-center study at Harvard Medical School's Dana-Farber Cancer Institute, it has been found at the 1.5 year post-transplant timepoint, that T-cell depleted transplants overall performed equally to conventional bone-marrow transplantation as measured by survival and quality of life. Larger multi-center studies are now underway to verify this finding.
Bibliography
- Graft-vs.-Host-Disease by Ferrara et al. (2nd ed.) published by Marcel Dekker is somewhat out of date, but still a nice bound volume.
- Example journals that publish current research on graft-versus-host-disease include The Biology of Blood and Marrow Transplantation, Journal of Clinical Investigation, Journal of Experimental Medicine, Blood, Journal of Immunology, Nature Immunology, Nature Medicine, Immunity, and Transplantation.
Related topics
- Transplantation
- Transplant rejection, also known as "host-verses-graft disease"
- Immunology
- Cancer
External links
- National Marrow Donor Program (http://www.marrow.org/PHYSICIAN/improved_management_gvhd.html)