Graft-versus-host disease (GVHD) is a common complication following an allogeneic transplant.
Symptoms of acute graft-versus-host-disease are primarily the result of damage to the liver, skin and the gastrointestinal tract. The disorder may also target the hematopoietic system, bone marrow, and the lungs. Chronic graft-versus-host-disease can also cause damage to the connective tissue. Acute graft-versus-host-disease usually presents within three to four weeks of transplantation with a painful, pruritic rash . In the most severe cases symptoms may include fever, erythroderma, and peeling of the skin. Liver involvement in graft versus host disease is measured by the bilirubin level.
Further symptoms of graft-versus-host-disease include:
There is no validated diagnostic blood test for acute graft-versus-host-disease. Workup of patients suspected of having acute graft-versus-host-disease should begin with a complete history and physical. The history of recent transplantation or transfusion is essential for diagnosis. The time of symptom appearance will designate acute from chronic disease. Physical examination will show distinctive rash, red raised rash primarily of face, palms, soles, and upper trunk. Jaundice may be present with liver involvement. Lesions, inflammatory or lichen-like, may occur on the oral mucosa. Conjunctivitis will also be apparent.
Workup should also include the following studies:
The primary intervention for acute graft-versus-host-disease is prevention. A 6 month course of cyclosporin A or tacrolimus, together with a short-course of methotrexate, should precede or follow transplantation. Antithymocyte globulin (ATG) may also be given prophylactically . Better typing and correlation of donor and host to prevent dissimilarities may do much to preventing the disease. Treatment with high-dose systemic steroids is still the primary therapy of graft versus host disease after more than 25 years. However, the complete response rate is only about 35%.
If chronic graft versus host disease persists:
In efforts to improve the survival rate, the addition of antithymocyte globulin, CD5-immunotoxins, or interleukin-2 antagonists have not been effective. Further research and the development of new therapies are needed. The use an anti-TNFα agents, infliximab or etanercept, are being studied to treat steroid-refractory graft versus host disease .
If the graft-versus-host-disease is severe, stage 4, or requires intense immunosuppression, the patient is susceptible to severe infections that may result in death. Increased susceptibility to infection, particularly Streptococcus pneumonia and Haemophilus influenzae pneumonia, occurs in 50% of patients with acute graft-versus-host-disease. The risk of bacteremia and septicemia is significantly increased in those with chronic graft-versus-host-disease. Treatment with azathioprine in these patients also increases the risk of secondary or recurrent neoplasms. Scleroderma like lesions associated with the chronic form of the disease can cause contractures of joints, affecting movement and ability to perform normal activities.
Transfusion-associated graft-versus-host-disease may have the frequent and possibly fatal complication of bone marrow aplasia. Irradiating blood products before transfusion can prevent this complication. Chronic graft-versus-host-disease may produce lichen planus in the oral cavity. There is a higher risk of these lesions becoming malignant. These oral cancers may have a more aggressive progress and a poorer prognosis.
The severity of acute graft-versus-host-disease is predictive of mortality rates. Outcomes for the disease are also determined by the patient’s response to treatment. Significantly higher mortality rates are seen in patients not responding to treatment or having progression of symptoms despite treatment. This rate may be as high as 75%, compared to 20-25% in those who respond well to treatment .
Graft-versus-host-disease occurs only in individuals who have received transplantations, especially of hemopoietic cells from a donor with remnants of the donor T-cells. Symptoms occur when these T-cells recognize the recipient’s tissues as foreign, inflammation and ulceration results. Recipient tissues, particularly skin, liver, and gastrointestinal, are damaged from this process.
Graft-versus-host-disease occurs in 7 to 10% of transplant recipients. The incidence may be as high as 50% in patients receiving stem-cell or bone marrow transplantation . The rate of chronic graft-versus-host-disease is lower in children than in adults.
Acute graft-versus host disease is a substantial post-transplantation problem and is the primary cause of mortality in these patients. Following transplantation, T-cells in the graft tissue, blood, organ, or bone marrow, attack the tissues of the recipient, after identifying host cells as foreign proteins. Even histo-compatible identical donors, siblings or unrelated donors, have minor antigens that are not compatible. Remnant donor T-cells proliferate and become effector cells which identify cells of the recipient as foreign proteins and attack them . This process leads to damage to the recipient’s tissue, especially dermal, gastrointestinal, and liver tissue. This then prompts the recipient’s body to produce inflammatory leukocytes and cytokine. Graft-versus-host-disease occurs in a three step process . The first step actually occurs prior to transplantation. This step involves chemotherapy and/or irradiation of the recipient in preparation for transplantation or to treat an underlying neoplasm or disease. These treatments cause the initial damage to the recipient’s liver, skin, and intestinal mucosa. Step two occurs with the activation and proliferation of the donor T-cells that have been introduced into the recipient’s system through the transplantation or transfusion process. These cells then attack the already damaged recipient tissues. The third phase is the response of the recipient’s immune system with the secretion of inflammatory leukophages and cytokines resulting in an aggressive inflammatory reaction.
Chronic graft-versus-host-disease mimics autoimmune diseases. The process is essentially the same as in acute graft versus host disease but has a delayed development and extended course. The exact reason for this delay or extension of symptoms in the chronic form is not yet clearly understood. Chronic graft-versus-host-disease affects most organs of the body. Skin and oral symptoms are the most common. Eyes, gastrointestinal mucosa, lungs, joints, and liver are often affected as well.
The primary intervention for acute graft-versus-host-disease is prevention. A 6 month course of cyclosporin A or tacrolimus, together with a short-course of methotrexate, should precede or follow transplantation. Better typing and correlation of donor and host to prevent dissimilarities may do much to preventing the disease.
Graft-versus-host-disease (GVHD) is a common complication in the transplantation of cells, tissue, or organs. It is most often associated with stem cell or bone marrow transplantation, or blood transfusions . Graft-versus-host-disease is a progressive systemic disorder involving tissue damage to various organs, particularly, liver, skin and intestinal mucosa, of the recipient’s body. Graft-versus-host-disease is an immune response disorder caused by an adverse interaction between the T-cells of the donor graft and the recipient’s tissue . The disorder occurs when residual donor T-cells in the graft are activated and attack recipient tissues primarily the skin, liver, gastrointestinal tract, and lungs. There are two forms of the disease, acute and chronic. Acute graft-versus-host-disease presents within 20 to 40 days of transplantation . Chronic graft-versus-host-disease occurs more than 100 days after transplantation and includes additional symptomology.
Acute graft-versus-host-disease is staged from 1 to a high of 4. Patients with grade 4 graft versus host disease usually have a poor prognosis. The occurrence and severity of the disorder depends on the source of donor graft . The incidence is significantly higher with unrelated donors than in related/sibling donors.
What is graft-versus-host-disease?
Graft-versus-host-disease (GVHD) is a complication that can occur after transplantations, stem cell or bone marrow transplants, and transfusions, in which the newly transplanted donor cells attack the transplant recipient's tissues. It results is inflammation, ulceration, and damage to the patient’s skin, liver, and mucous membranes of the mouth, esophagus, and intestines. There are two types of graft-versus-host disease, acute and chronic. Symptoms in both forms may be mild or severe. Acute graft-versus-host-disease happens within 3 months of transplant. The chronic form occurs more than 3 months after transplant.
What are the symptoms of graft-versus-host-disease?
Symptoms of acute graft-versus-host-disease include:
Symptoms of chronic graft-versus-host-disease are:
What causes graft-versus-host-disease?
Graft-versus-host disease is caused when T-cells in the donor graft are activated after transplantation. Once activated these cells mistakenly recognize the cells of the recipient as foreign proteins and attack then. The host tissue, primarily skin, mucous membrane of mouth and intestinal tract, and liver are damaged. The recipient’s body responds with a system wide inflammatory reaction resulting in swelling, ulceration, and cellular death. Graft-versus-host disease does not occur when someone receives his or her own cells during a transplantation or transfusion.
Who gets graft-versus-host-disease?
Tissue and cells from possible donors are checked before the transplantation. Donor and recipient are matched as closely as possible. The closer the match the less likely graft versus host disease will occur. The chance of graft-versus-host-disease is:
At highest risk of developing graft-versus-host-disease are:
How is it diagnosed?
There is no specific tests for the diagnosis of graft-versus-host disease. However, a biopsy of the skin, mucus membranes, intestinal tract, or liver may help confirm the diagnosis. Some lab and imaging tests can be helpful in the monitoring of the disease and its complications.
How is graft-versus-host-disease treated?
After a transplant, usually, all recipients take medications to suppress their immune system. This reduces the incidence and severity of graft versus host disease. These and other drugs are continued after transplantation to continue prevention. The primary treatment once graft-versus-host disease has been diagnosed is high-dose corticosteroids like prednisone. Approximately a third of patients do not respond to these drugs. There are other drugs now being used in resistant cases.
What are the complication of graft versus host disease?
During the acute phase of graft-versus-host disease, patients are at risk for dehydration due to severe diarrhea and vomiting. Severe anemia may also result from gastrointestinal bleeding. Graft-versus-host-disease may cause permanent damage to affected tissues, liver, skin, mucous membranes of intestinal tract, and lungs. This damage is a result of inflammation. Those with the disorder are at risk for severe, often life threatening infections as a result of high-dose, long-term immunosuppressive drugs.
What can we do to prevent the complications?
In the acute phase, resting of the gastrointestinal tract may be necessary to reduce and resolve the diarrhea. However, maintaining hydration is crucial. A gradual progressive diet is recommended, clear liquids to bland diet. Avoid exposure to the sun and use greater than SPF 30 sunblock. Good skin care is essential to prevent skin infections. Moisturizing lotions or creams help prevent skin breakdown. Avoid unnecessary exposure to infections while they are receiving highly immunosuppressive treatment. Regular exercise to maintain muscle tone and activity tolerance.