Graft-vs.-Host Disease

Graft-vs.-host disease

Description

Graft-vs.-host disease is a response by the immune system that occurs when cells from a blood or bone marrow donor attack those of the recipient. The only transplanted tissues that contain 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 in cancer patients whose own bone marrow has been destroyed by radiation therapy or chemotherapy .

Blood transfusion graft-vs.-host disease affects mostly the blood. Blood cells perform three functions: carrying oxygen, fighting infections, and clotting. All of these functions are decreased in a transfusion graft-vs.-host reaction, leading to anemia (lack of red blood cells in the blood), reduced resistance to infections, and increased bleeding. The reaction occurs 4-30 days after the transfusion.

The tissues most affected by bone marrow graft-vs.-host disease are the skin, the liver, and the intestines. One of these forms of tissue is affected in nearly half of the patients who receive bone marrow transplants.

Bone marrow graft-vs.-host disease comes in both an acute and a chronic form. The acute form appears within two months of the transplant, while 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 (alopecia ), 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 that inhibit the immune response . Patients can die of liver failure, infection, or other severe disturbances of their system.

Causes

Cells from the donor who has an active immune system may be transplanted along with the organ or tissue into the host who has a suppressed immune system. These transplanted cells attack the host's body, causing graft-vs.-host disease. Substances made in the body called cytokines are thought to play a role in the development of this reaction. Cytokines are protein substances made by cells that affect other cells.

Even if the donor and recipient are well matched, graft-vs.-host disease can still occur. There are many different components involved in generating immune reactions, and all people (except identical twins) are different. Testing can often find donors who match all the major components, but there are many minor ones that will always be different. Making a match between a donor and recipient depends upon the urgency of the need for a transplant and the chance that a suitable donor will be found.

Treatments

Both the acute and the chronic diseases are treated with cortisone-like drugs, immunosuppressive agents, or with antibiotics and immune chemicals from donated blood (gamma globulin). Cyclosporine and prednisone are two immunosuppressive drugs that are often used, and methotrexate may enhance efficacy. Another way to prevent graft-vs.-host disease is, before transplantation, rid donor bone marrow of the immune cells (T cells) that would attack the recipient's body. Another possibility to avoid complications in bone marrow transplantation is to cleanse the bone marrow of cancer cells and use the patient's own cells to grow more bone marrow. Cancer cells that reside in the bone marrow may be removed, leaving behind only those cells that are needed to grow new blood cells (stem cells). These stem cells from the patient can be grown and returned back to the patient.

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.

New directions in research may help to solve the problem of graft-vs.-host disease. A potential source for new stem cells is the umbilical cord. Cells from this area do not give such strong immune reactions and may be useful for re-establishing cell populations. Another potential is to use genetically engineered cells to correct genetic defects in stem cells within the marrow.

Alternative and complementary therapies

Alternative and complementary therapies range from herbal remedies, vitamin supplements, and special diets to spiritual practices, acupuncture, massage, and similar treatments. When these therapies are used in addition to conventional medicine, they are called complementary therapies. When they are used instead of conventional medicine, they are called alternative therapies.

Complementary or alternative therapies are widely used by people suffering with illness. Good nutrition and activities, such as yoga, meditation, and massage, that reduce stress and promote a positive view of life have no unwanted side effects and appear to be beneficial. Alternative and experimental treatments are normally not covered by insurance.

Special concerns

If graft-vs.-host disease is suspected as a complication to a cancer treatment, a skin punch biopsy may be performed to confirm this diagnosis. This is a relatively minor procedure in which the skin is anesthetized in a local area and a small piece is removed for testing in the laboratory.

Infection with one particular virus, called cytomegalovirus (CMV), is so likely a complication of graft-vs.-host disease that some experts recommend treating it in advance, using ganciclovir or valacyclovir.

It is an interesting observation that patients with leukemia 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). The grafted cells develop a tolerance to the recipient's body after 6-12 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 disease, or rejection, occurs when the recipient's immune system is strong enough to attack the transplant. This is also a common occurrence 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.

See also Bone marrow transplantation; Transfusion therapy

Resources

BOOKS

Anderson, William L. Immunology. Madison, CT: Fence Creek Publishing, 1999.

Armitage, James O. "Bone Marrow Transplantation." In Harrison's Principles of Internal Medicine, edited by Kurt Isselbacher, et al. New York: McGraw-Hill, 1998, pp.726-727.

Janeway, Charles A., et al. Immunobiology:The Immune System in Health and Disease. New York, NY: Current Biology Publications; London, England: Elsevier Science London/Garland Publishing, 1999.

Menitove, Jay E. "Blood Transfusion." In Cecil Textbook of Medicine, edited by J. Claude Bennett and Fred Plum. Philadelphia: W. B. Saunders, 1996, p. 896.

Rappeport, Joel. "Bone Marrow Transplantation." In Cecil Textbook of Medicine, edited by J. Claude Bennett and Fred Plum. Philadelphia: W. B. Saunders, 1996, p.975.

Roitt, Ivan and Arthur Rabson. Really Essential Medical Immunology. Malden, MA: Blackwell Science, 2000.

Ruscetti, Francis W., Jonathan R. Keller, and Dan L. Longo."Hematopoiesis." In Harrison's Principles of Internal Medicine, edited by Kurt Isselbacher, et al. New York: McGraw-Hill, 1998.

Widmann, Frances K., and Carol A. Itatani. An Introduction to Clinical Immunology and Serology. Philadelphia, PA: F.A. Davis Company, 1998.

Wier, Donald M. and John Stewart. Immunology. New York, NY: Churchill Livingston, Inc., 1997.

OTHER

Complementary and Alternative Medicine Web site for the American Cancer Society. <http:cancer.org/alt_therapy/index.html>.

University of Michigan Patient Education Resource Center (PERC). <http://www.cancer.med.umich.eduhtm>.

University of Michigan Transplant Center. <http://www.med.umich.edu/trans/public/>.

J. Ricker Polsdorfer, M.D.

Jill Granger, M.S.

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 that suppresses an immune response.

Lesion

—Localized disease or damage.

Scleroderma

—Progressive disease of the connective tissue of the skin and internal organs.