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Graft-versus-host disease (GVHD) is a possible complication of any stem cell transplant that uses stem cells from either a related or an unrelated donor (an allogeneic transplant). To understand GVHD, it is helpful to compare it to a more familiar concept: rejection following a solid organ transplant.

For example, in a heart transplant, it's possible that the transplant patient's immune system will decide that the transplanted heart does not belong in the body, and immune system cells will attack the heart. When this happens, doctors say that the patient's body is rejecting the heart.

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).

There are two kinds of GVHD: acute and chronic. Acute GVHD appears within the first three months following transplantation. Signs of acute GVHD 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.

Chronic GVHD is ranked by doctors based on its severity: stage (or grade) 1 is mild, 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.

Why does GVHD develop?

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). In all other types of stem cell transplants, the donor's immune system is a very good, but not perfect, match with the recipient's immune system.

Even when transplant doctors talk of a "perfect match" between a donor and a patient, they are only saying that a handful of key immune system characteristics or "markers" are matched up. These matched markers are the most important markers for transplantation purposes, but several other, less significant markers may remain unmatched.

It is these small differences that 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.

Preventing GVHD

To prevent GVHD, some transplant doctors choose to remove all or some of the T-cells from the donated stem cells before they are given to the recipient. This is not universally done, however, because doing so increases the chance that the transplant will fail, that is, that none of the donated stem cells will begin to grow in the recipient's body, leaving the recipient with no immune system whatsoever. This is called graft failure, which is a very serious complication that has few treatment options.

Eliminating T-cells may also cancel the benefits of GVHD. Although full-blown GVHD is not desirable, mild GVHD is actually beneficial to the patient. In the days and weeks following a transplant, signs of mild GVHD mean that the donor's stem cells have begun to grow in the recipient's body. Also, the T-cells that cause GVHD can also act to destroy any cancerous cells in the recipient's marrow and blood that may have survived the pre-transplant chemotherapy.

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.

Treating GVHD

If it develops, acute GVHD is treated with various combinations of the immunosuppressive drugs mentioned above. These drugs are almost always effective in reducing acute GVHD, and can often eliminate it completely. However, some patients may not be helped by these drugs and their acute GVHD may persist and develop into chronic GVHD. And unfortunately, acute GVHD can also be fatal in some instances.

Chronic GVHD is treated mainly with steroids such as cyclosporine, prednisone, and ozothioprine. In addition, transplant recipients with chronic GVHD may receive eye drops if the disease is affecting the eyes. Recipients with chronic GVHD affecting the mouth must maintain good oral hygiene to prevent infections. Patients with stomach GVHD must avoid acidic foods and they may be placed on special diets.