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Graft vs. Host Disease Definition
Graft vs. Host Disease – a life-threatening condition in which the immune cells (leukocytes and lymphocytes) contained in allogeneic transplanted BONE MARROW (the graft, from a donor source) produce antibodies that attack other organs in the organ transplant recipient’s body (the host).
BONE MARROW TRANSPLANTATION(or BLOOD STEM CELL transplantation) is the primary treatment for cancers of the BLOOD such as LEUKEMIA, lymphoma, and MULTIPLE MYELOMA. Doctors may also use bone marrow transplantation to treat some types of cancer that do not respond to other therapies, severe aplastic ANEMIA, and severe SICKLE CELL DISEASE.
Graft vs. host disease is not a threat with autologous (self) bone marrow transplantation, which re-infuses blood stem cells previously withdrawn from the person. The condition occasionally develops after solid ORGAN TRANSPLANTATION and in IMMUNOCOMPROMISED people who receive BLOOD TRANSFUSIONS.
The immune cells of the transplanted bone marrow generate antibodies that commonly attack the recipient’s LIVER, gastrointestinal tract (especially the STOMACH and SMALL INTESTINE), and SKIN. Damage can be rapid and severe. When the condition involves multiple organs, as is common, catastrophic multiple system failure is very possible. Graft vs. host disease accounts for more deaths after 100 days past the bone marrow transplantation than any other cause, including the cancer under treatment.
Symptoms and Diagnostic Path
Acute graft vs. host disease occurs within 100 days after the transplantation. About 30 percent of bone marrow transplant recipients experience acute symptoms, which may include
Chronic graft vs. host disease develops or continues beyond 100 days from transplantation, though typically chronic disease tends to first manifest between 3 and 12 months after the transplant. The perpetual attacks that are the hallmark of chronic graft vs. host disease result in fibrotic (SCAR-related) changes to the skin, liver, and LUNGS. About 70 percent of people who receive bone marrow transplants experience some degree of chronic symptoms, which typically include
- dry, itchy skin
- discolored or taut skin
- HAIR loss or graying
- weight loss
- shortness of breath with exertion (DYSPNEA)
- chronic fatigue
- dry eyes and mouth
The diagnostic path includes blood tests to measure blood cell types and counts, ANTIBODY levels, and liver enzymes. In particular, CD-4+ and CD-8+ T-lymphocytes are abundant. Tissue biopsies also show evidence of damage due to the immune attack. Doctors classify graft vs. host disease into four stages, according to the severity of symptoms; stage 1 is the mildest and stage 4, the most severe.
Treatment Options and Outlook
At present the most successful treatment is IMMUNOSUPPRESSIVE THERAPY. Ideally, prophylactic immunosuppression prevents graft vs. host disease. When symptoms occur, immunosuppression can minimize the consequences and limit damage. Immunosuppression itself carries significant risk, however. The risk for infection, especially an OPPORTUNISTIC INFECTION the IMMUNE SYSTEM could normally keep at bay, is very high. CORTICOSTEROID MEDICATIONS, the cornerstone of immunosuppressive therapy, cause serious side effects with long-term, systemic use. As well, some immunosuppressive agents are chemotoxic (they work by killing cells) and have harmful side effects. The balance between sufficient immune suppression and adequate immune function is delicate.
Other treatment options include MONOCLONAL ANTIBODIES (MABS), which bind with the ANTIGENreceptors on the cell membrane surfaces of the cells in the organ. However, the body may develop antibodies against the MAbs. Though the first treatment is successful, subsequent efforts with the same MAbs will initiate an immune attack against the MAbs. A number of clinical trials are exploring investigational treatments for graft vs. host disease. A key challenge in treatment is that, although doctors fully understand what happens during graft vs. host disease, the mechanisms by which events occur remain unknown.
|ACUTE GRAFT VS. HOST DISEASE STAGING|
|Stage||Degree of Severity||Symptoms|
|1||mild||SKIN RASH affecting less than 25 percent of the skin surface, often starting on the hands and feet|
no other symptoms
|2||moderate||skin rash affecting more than 25 percent of the skin surface|
mild gastrointestinal discomfort and DIARRHEA
|3||severe||extensive SUNBURN-like rash over most of the body|
STOMACH discomfort, abdominal cramping, diarrhea
frequent or chronic INFECTION
moderate jaundice and LIVER dysfunction
|4||life threatening||skin blisters and peeling skin over most of the body|
severe jaundice and significant liver dysfunction or LIVER FAILURE
serious INFECTION or OPPORTUNISTIC INFECTION
malabsorption of NUTRIENTS
Risk Factors and Preventive Measures
Anyone who has bone marrow transplantation is at risk for graft vs. host disease. Optimal matching of HUMAN LEUKOCYTE ANTIGENS (HLAS) before transplantation provides the most successful circumstance for preventing graft vs. host disease. When precise HLA matching is not possible, screening for and selectively removing some T-cell lymphocytes (CD-4+ and CD-8+) from the donor organ that carry antibodies likely to attack the recipient can reduce the risk for graft vs. host disease. The risk for graft vs. host disease is also higher for people who receive blood stem cells extracted from donated blood (rather than from bone marrow donation), except cord stem cells extracted from umbilical blood.