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What is GVHD
What is HLA Matching
Christopher Reeve

Graft Vs. Host Disease

Graft vs. host disease or popularly called GVHD is nothing special but it is an immune attack on the recipient by the cells from a donor.

In other words, GVHD is a possible complication in any form, from any stem cell transplant that uses stem cells from either a related or an unrelated donor (an allogeneic transplant). It may sound bit difficult to understand the concept. So, to understand GVHD, it is helpful to compare it to a more familiar concept: rejection following a solid organ transplant in a human body.

For example, in a kidney transplant, it's possible that the transplant patient's immune system will decide that the transplanted kidney does not belong in the body, and immune system cells will attack the kidney as foreign organ. When this happens, doctors usually say that the patient's body is rejecting the transplanted kidney. In stem cell transplants, a similar reaction can occur, but in the other direction. In a stem cell transplant, the transplanted cells recreate the donor's immune system in the body of the recipient. (Remember, to prepare for a transplant, a recipient has had his or her own defective marrow and immune system cells destroyed by chemotherapy.) GVHD is the term used when this donated immune system (the graft) begins to attack the recipient's body (the host). That is the main concept behind this medical jargon.

In medical terms, there are two kinds of GVHD: acute and chronic. An acute GVHD appears within the first three months following transplantation. Signs of acute GVHD may cause an irritation or allergy and generally include a reddish skin rash on the hands and feet that may spread and become more severe, with peeling or blistering skin. Acute GVHD can also affect the stomach and intestines, in which case cramping, nausea, and diarrhea are present. Yellowing of the skin and eyes (jaundice) indicates that acute GVHD has affected the liver.

On the other hand, chronic GVHD is ranked by doctors based on its severity, like stage (or grade) 1 is mild, while stage (or grade) 4 is severe. Chronic GVHD develops three months or later following transplantation. The symptoms of chronic GVHD are similar to those of acute GVHD, but in addition, chronic GVHD may also affect the mucous glands in the eyes, salivary glands in the mouth, and glands that lubricate the stomach lining and intestines.

Both forms of GVHD bring with them an increased risk of infections, either because of the process itself or its treatment with cortisone-like drugs and immunosuppressives. Patients can die of liver failure, infection, or other severe disturbances of their system.

In only two kinds of stem cell transplants are the donor and recipient 100 percent matched. One such instance is when the donor and recipient are identical twins, and the other case is when the donor and the recipient are the same person (an autologous transplant). Usually, transplant specialists find out the perfect match (of course by matching the key immune system characteristics) between a donor and a patient. In actual sense, few key characteristics are matched up, while others remain unmatched, and these unmatched markers or characteristics can lead to GVHD.

While a donor's immune system is establishing itself in the recipient's body, T-cells in the transplanted stem cell graft may begin to attack the recipient's body. T-cells are a type of white blood cell present in any stem cell collection. They are one of the most powerful cells of the immune system, and they act directly on foreign materials in the body to kill them. GVHD is thought to occur when there is enough of a difference between the donor and recipient that the T-cells from the donor determine that the recipient's body is foreign.

How to prevent it?

The standard way to prevent GVHD is to give drugs that suppress the immune system to the transplant patient before and after the transplant. Immunosuppressive drugs (so-called because they suppress the immune system) include cyclosporine, methotrexate, and steroids. Doctors are careful when using these drugs, because they also increase the risk that the recipient will become infected with harmful viruses, bacteria, and fungi. These drugs may also cause serious side effects such as organ damage, especially to the kidneys.

For recipients of blood transfusions who are especially likely to have graft-vs.-host reactions, the red blood cells can safely be irradiated (using x rays) to kill all the immune cells. The red blood cells are less sensitive to radiation and are not harmed by this treatment.

Much current research is directed towards solving the problem of GVHD. There are efforts to remove the immunogenic cells from the donor tissue, and there are also attempts to extract and purify bone marrow cells from the patient before treating the cancer. These cells are then given back to the patient after treatment has destroyed all that were left behind.