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Pronunciations azathioprine corticosteroid cyclophosphamide cyclosporine dexamethasone diabetes mellitus hepatitis hirsutism histocompatibility lymphocytes lymphoma macrolide methotrexate osteoporosis pancreas prednisone sepsis T3

Organ transplantation, unlike a blood transfusion, involves major surgery, the use of drugs to suppress the immune system (immunosuppressants), and the possibility of transplant rejection and serious complications, including death. However, for people whose vital organs malfunction irreversibly, organ transplantation may offer the only chance of a normal life or of survival.

Tissue Matching

Matching the tissues of an organ donor and those of the recipient is desirable because the immune system normally attacks foreign tissue (see Biology of the Immune System: Introduction), including transplants. This reaction is called rejection. However, tissue matching may have to be balanced with other factors that affect the quality of the transplant, such as the time involved in reaching the recipient. Some people are too ill to wait for a highly compatible donor. For organs (such as the heart) that cannot be donated by a living family member, a highly compatible donor is rarely available. With the use of immunosuppressants, the success of transplantation is less affected by the compatibility of the donor. Consequently, transplants, even of organs (such as a kidney) that may be donated by a living family member who is highly compatible, may come from less compatible donors. Nonetheless, doctors try to find a donor whose tissue type matches the recipient's tissue type as closely as possible. A close match reduces the severity of rejection and improves the long-term outcome for the recipient.

Tissue type is determined by molecules on the surface of every cell in the body. These molecules are called human leukocyte antigens (HLA) or the major histocompatibility complex. Each person has unique HLAs. When a person receives a transplant, the HLAs on the cells of the transplant signal the body that the tissue is foreign, stimulating an immune response.

For blood transfusions, matching is relatively simple, because red blood cells have only three main antigens on their surface—A, B, and Rh. For organ transplantation, many antigens are involved.

The recipient's blood is screened for antibodies against the tissues of the specific potential donor. The body may produce such antibodies in response to a blood transfusion, a previous transplantation, or a pregnancy. If these antibodies are present, transplantation is usually not performed, because immediate, severe rejection often results.

Suppression of the Immune System

Even if tissue types are closely matched, transplanted organs, unlike transfused blood, are usually rejected unless measures are taken to prevent rejection. Rejection results not only in destruction of the transplanted organ but also in fever, chills, nausea, fatigue, and sudden changes in blood pressure. Rejection, if it occurs, usually begins soon after transplantation but can occur after weeks, months, or even years. Rejection can be mild and easily controlled or severe, worsening despite treatment.

Rejection can usually be controlled by using drugs called immunosuppressants, which suppress the immune system and the body's ability to recognize and destroy foreign substances. With the use of these drugs, transplantation is more likely to be successful. However, while immunosuppressants suppress the immune system's reaction to the transplanted organ, they also reduce the ability of the immune system to fight infections and perhaps to destroy cancer cells. Thus, transplant recipients are at increased risk of developing infections and certain cancers.

Many different types of immunosuppressants can be used to prevent or control rejection. Most of them, including corticosteroids, suppress the immune system as a whole. Antilymphocyte globulin, antithymocyte globulin, and monoclonal antibodies suppress only specific parts of the immune system.

Immunosuppressants must be taken indefinitely. However, high doses are usually necessary only during the first few weeks after transplantation or during an episode of rejection. After that, smaller doses can usually prevent rejection. At the first sign of rejection, doctors increase the dose of the immunosuppressant, change the type of immunosuppressant, or use more than one immunosuppressant.

Sometimes radiation is directed at the transplant and surrounding tissue to suppress the immune system. Before bone marrow transplantation in people with leukemia, radiation of the whole body is necessary to destroy the bone marrow, which is producing cancer cells. Radiation of all lymph nodes (total lymphatic irradiation) appears to be a safe, effective way to suppress the immune system, but this treatment is still being studied.

Drugs Used to Prevent Transplant Rejection Type Drug Possible Side Effects Comments Corticosteroids (potent anti-inflammatory drugs that suppress the immune system as a whole)   Dexamethasone Prednisolone Prednisone High blood sugar levels (as occur in diabetes mellitus), muscle weakness, osteoporosis, water retention, stomach ulcers, a puffy face, fragile skin, and excess hair on the face Given by vein in a high dose at the time of transplantation; then gradually reduced to a maintenance dose given by mouth, usually indefinitely Globulins (natural substances produced by the body that suppress specific parts of the immune system)   Antilymphocyte globulin Antithymocyte globulin Severe allergic (anaphylactic) reactions with fever and chills, usually occurring only after the first or second dose Given by vein; used with other immunosuppressants so that the other immunosuppressant can be started later or its dose can be reduced (to reduce side effects) Macrolide immunosuppressants (drugs that suppress specific parts of the immune system)   Sirolimus Increased cholesterol levels, high blood pressure, rash, anemia, joint pain, diarrhea, low potassium levels, and increased risk of lymphoma Taken by mouth and used with corticosteroids or cyclosporine in people who have received a kidney transplant   Tacrolimus Tremor, headache, diarrhea, high blood pressure, nausea, liver and kidney damage, insomnia, an enlarged heart, and increased risk of lymphoma Given by vein or by mouth at the time of transplantation or later; used as an alternative to cyclosporine in people who have received a liver transplant Mitotic inhibitors (drugs that suppress cell division and thus the production of white blood cells)   Azathioprine Fatigue, increased risk of infection, a tendency to bleed, nausea, vomiting, hepatitis (rarely), and a low white blood cell count Given by vein or by mouth at the time of transplantation and often continued indefinitely sometimes at a reduced dose; may be used with cyclosporine   Cyclophosphamide Fatigue, increased risk of infection, a tendency to bleed, nausea, vomiting, hair loss, bladder inflammation (cystitis) with bleeding, and infertility Given by vein or by mouth; used for people who cannot tolerate azathioprine; used in high doses in people who have received a bone marrow transplant   Methotrexate Fatigue, increased risk of infection, a tendency to bleed, nausea, vomiting, mouth sores, digestive upset, general feeling of illness, chills, fever, and dizziness Given by mouth or injected in muscle Monoclonal antibodies (substances that target and suppress specific parts of the immune system)   Basiliximab Daclizumab Infliximab Muromonab (OKT3) Severe allergic (anaphylactic) reactions, fever, shaking (rigors), muscle and joint pain, irritation of the digestive tract, seizures, and drug tolerance (the drug becomes less effective for subsequent rejection episodes); severe side effects usually only occur after the first few doses Given by vein at the time of a rejection episode or transplantation Fungal metabolite (a substance that is produced by a fungus and that inhibits the activity of T lymphocytes)   Cyclosporine Liver and kidney damage, high blood pressure, tremor, enlarged gums, excessive hairiness (hirsutism), and increased risk of cancer Given by vein at first, then by mouth; usually given with azathioprine or prednisone Others   Glatiramer acetate Inflammation at the site of injection, chest pain, weakness, infection, pain, nausea, and joint pain Injected under the skin; used in people who have received liver transplants   Mycophenolate mofetil Diarrhea, a blood infection (sepsis), nausea, vomiting, and increased risk of lymphoma Given by vein at first, then by mouth; used with corticosteroids or cyclosporine

Last full review/revision February 2003