Graft-vs.-Host Disease

Graft-vs.-Host Disease

 

Definition

Graft-vs.-host disease is an immune attack on the recipient by cells from a donor.

Description

The main problem with transplanting organs and tissues is that the recipient host does not recognize the new tissue as its own. Instead, it attacks it as foreign in the same way it attacks germs, to destroy it.
If immunogenic cells from the donor are transplanted along with the organ or tissue, they will attack the host, causing graft vs. host disease.
The only transplanted tissues that house enough immune cells to cause graft vs. host disease are the blood and the bone marrow. Blood transfusions are used every day in hospitals for many reasons. Bone marrow transplants are used to replace blood forming cells and immune cells. This is necessary for patients whose cancer treatment has destroyed their own bone marrow. Because bone marrow cells are among the most sensitive to radiation and chemotherapy, it often must be destroyed along with the cancer. This is true primarily of leukemias, but some other cancers have also been treated this way.

Causes and symptoms

Even if the donor and recipient are well matched, graft-vs.-host disease can still occur. There are many different elements involved in generating immune reactions, and each person is different, unless they are identical twins. Testing can often find donors who match all the major elements, but there are many minor ones that will always be different. How good a match is found also depends upon the urgency of the need and some good luck.
Blood transfusion graft-vs.-host disease affects mostly the blood. Blood cells perform three functions: carrying oxygen, fighting infections, and clotting. All of these cell types are decreased in a transfusion graft-vs.-host reaction, leading to anemia (lack of red blood cells in the blood), a decrease in resistance to infections, and an increase in bleeding. The reaction occurs between four to 30 days after the transfusion.
The tissues most affected by bone marrow graft-vs.-host disease are the skin, the liver, and the intestines. One form or the other occurs in close to half of the patients who receive bone marrow transplants.
Bone marrow graft-vs.-host disease comes in an acute and a chronic form. The acute form appears within two months of the transplant; the chronic form usually appears within three months. The acute disease produces a skin rash, liver abnormalities, and diarrhea that can be bloody. The skin rash is primarily a patchy thickening of the skin. Chronic disease can produce a similar skin rash, a tightening or an inflammation of the skin, lesions in the mouth, drying of the eyes and mouth, hair loss, liver damage, lung damage, and indigestion. The symptoms are similar to an autoimmune disease called scleroderma.
Both forms of graft-vs.-host disease 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.

Treatment

Both the acute and the chronic disease are treated with cortisone-like drugs, immunosuppressive agents like cyclosporine, or with antibiotics and immune chemicals from donated blood (gamma globulin). Infection with one particular virus, called cytomegalovirus (CMV) is so likely a complication that some experts recommend treating it ahead of time.

Prognosis

Children with acute leukemias have greatly benefited from the treatment made possible by bone marrow transplantation. Survival rates have climbed by 15-50%. It is an interesting observation that patients who develop graft-vs.-host disease are less likely to have a recurrence of the leukemia that was being treated. This phenomenon is called graft-vs.-leukemia.
Bone marrow transplant patients who do not have a graft-vs.-host reaction gradually return to normal immune function in a year. A graft-vs.-host reaction may prolong the diminished immune capacity indefinitely, requiring supplemental treatment with immunoglobulins (gamma globulin).
Somehow the grafted cells develop a tolerance to their new home after six to 12 months, and the medications can be gradually withdrawn. Graft-vs.-host disease is not the only complication of blood transfusion or bone marrow transplantation. Host-vs.-graft or rejection is also common and may require a repeat transplant with another donor organ. Infections are a constant threat in bone marrow transplant because of the disease being treated, the prior radiation or chemotherapy and the medications used to treat the transplant.

Prevention

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 graft-vs.-host disease. 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.

Resources

Books

Armitage, James O. "Bone Marrow Transplantation." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.

Key terms

Anemia — Too few red blood cells, or too little hemoglobin in them.
Immunoglobulin — Chemicals in the blood that defend against infections.
Immunosuppressive — A chemical which suppresses an immune response.
Inflammation — The body's immune reaction to presumed foreign substances like germs. Inflammation is characterized by increased blood supply and activation of defense mechanisms. It produces redness, swelling, heat, and pain.
Lesion — Localized disease or damage.
Scleroderma — Progressive disease of the connective tissue of the skin and internal organs.
References in periodicals archive ?
But MSCs have also been found to have a number of other beneficial therapeutic properties, including their ability to modulate the immune system by inhibiting T-cell proliferation, eliminating graft-vs.
But they have also been found to have a number of other beneficial therapeutic properties, including their ability to modulate the immune system by inhibiting T-cell proliferation, eliminating graft-vs.
Recipient and donor factors influence the incidence of graft-vs.
The leukemia never returned, but she eventually contracted graft-vs.
These applications include treatment of phenytoin toxicity and of overdoses involving other highly protein-bound drugs, relief of the severe intractable itching that can torment patients with primary biliary cirrhosis, and treatment of graft-vs.
While our pivotal Phase III clinical trial of orBec for the Fast-Track indication of intestinal graft-vs.
Use of cord stem cells is rapidly expanding in bone marrow transplantation, where the immunologically naive cord blood cells carry a much lower risk of graft-vs.
The only complication Amador had was a rash due to the graft-vs.
The researchers selected only those cells that were incapable of attacking the recipients' own cells and causing graft-vs.
Despite the negative side effects from those treatments, nothing compared to the brutal suffering which occurred after he contracted graft-vs.
DOR's lead product, orBec(R) (oral beclomethasone diproprionate), is currently in a pivotal phase III clinical trial for the treatment of intestinal graft-vs.
Doctors will check his weight - it's going up - and also watch for symptoms of graft-vs.