Graft-versus-host disease

Graft-versus-host disease is a common complicationof allogeneic bone marrow transplantation. After bone marrowtransplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissuesof the transplantrecipient. Graft-versus-host disease can occur even when HLA-identical siblings 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 proteinsthat can be presented on the MHC.

While donor T-cellsare undesirable as effector cells of graft-versus-host-disease, they are valuable for engraftment by preventing the recipient's residual immune systemfrom rejecting the bone marrow graft (host-versus-graft). Additionally, as bone marrow transplantation is frequently used to cure malignantdisorders (most prominently the leukemias), donor T-cells have proven to have a valuable graft-versus-tumoreffect. 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.

Types

Clinically, graft-versus-host-disease is divided into acuteand chronicforms. The acute or fulminant form of the disease is observed within the first 100 days post-transplant, and the chronic form of graft-versus-host-disease is defined as that which occurs after 100 days. This distinction is not arbitrary: acute and chronic graft-versus-host-disease appear to involve different immune cellsubsets, different cytokineprofiles, and different types of target organ damage.

Classically, graft-versus-host-disease is characterized by selective damage to the liver, skinand mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs include the immune system(the hematopoietic system-- e.g. the bone marrowand the thymus) itself, and the lungsin 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 fungalinfection. Methotrexateand cyclosporinare common drugs used for GVHD prophylaxis. In a multi-center study (Lancet 2005 Aug 27-Sep 2;366(9487):733-41), disease-free survival at 3 years was not different between T cell depleted and T cell replete transplants.

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.

See also

• Transplantation
  • Transplant rejection, also known as "host-verses-graft disease"
• Immunology
  • Immunosuppression
• Cancer

External links

• National Marrow Donor Program

de:Graft-versus-Host-Reaktion

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Graft-versus-host+disease Wikipedia article Graft-versus-host disease.