Graft-versus-host reaction is an immunologic complication that can lead to graft rejection in allogeneic transplantation. Meanwhile, the reaction can be controlled by the prophylactic administration of immunosuppressants. Nevertheless, a mortality rate of ten percent still applies today.
What is the graft-versus-host reaction?
In a transplant, organic material is transplanted from a donor into a recipient. When the donor and recipient are not twins, the transplant is called an allogeneic transplant. The tissue of the recipient is not genetically identical to the tissue of the donor. Therefore, rejection can occur. In such cases, a graft-versus-host reaction is often present. In fact, this reaction is one of the most common complications of transplantation. It is a cytotoxic immunological reaction that the implanted or transfused immune cells in the graft undertake against the organism of the recipient. Especially the T-lymphocytes react against the transplant recipient. The literal translation of graft-versus-host reaction is graft-versus-host reaction. It plays a role primarily for bone marrow transplants and stem cell therapies, but is also observed in other transplants. There are four different severity levels of the reaction.
Causes
The cause of a graft-versus-host reaction is the transplantation of foreign immune cells. Immunologic cells are specialized cells from the bone marrow, spleen, or lymph nodes. Such cells can be contained in transplants, for example, and trigger cellular immune reactions in the organism of the transplant recipient. As part of the reaction, specific cytotoxic T cells are formed that are directed against the host. The risk for a complication such as graft-versus-host reaction depends on the immunological compatibility of the recipient and donor organism. The human leukocyte antigen determines this compatibility and should be as similar as possible. However, even when sibling donors with the same HLA are transplanted, graft-versus-host reactions of mild to moderate severity develop in more than one-third of cases. The stability of the recipient organism also influences the risk of reaction. Immune-healthy recipients usually degrade the transferred immune cells without complications. Immunocompromised hosts are unable to do so.
Symptoms, complaints, and signs
Symptoms of the graft-versus-host reaction depend on the severity. In immunocompromised individuals, severe conditions such as atrophy of lymphoid organs, gastrointestinal tract disorders, and skin lesions or cachexia are conceivable. The graft-versus-host reaction can thus even have a fatal outcome. Acute graft-versus-host reaction is the term used for a reaction in the first weeks after transplantation. The epithelial cells of the skin are affected by maculopapular exanthema or erythroderma. In the intestine, intestinal inflammation enteritis often presents with consequences such as diarrhea or painful bowel tenesmus. The liver reacts simultaneously with icterus, which can lead to liver failure. The chronic graft-versus-host reaction only sets in after about three months. Severe infections and mucosal changes in the gastrointestinal tract are its leading symptoms. In addition, the serous membranes of the skin and liver may be affected. In all forms, the reaction is expressed primarily in symptoms of the skin, liver, intestines, or eyes.
Diagnosis and course
The acute form of graft-versus-host reaction manifests histologically as lymphocytic infiltration. Cell damage and cell death are also present. Histological evidence of these circumstances has diagnostic value after transplantation. Because the symptomatology is relatively typical and is present in direct association with transplantation, diagnosis is relatively simple. The course depends on the severity of the reaction. Although, at the current state of science, medicine has ways to considerably reduce the risks of graft-versus-host reaction, the mortality rate from immunologic rejection for allogeneic transplantation is still currently about ten percent.
Complications
Various complications and medical conditions can result from graft-versus-host reaction.However, the further course depends on the manifestation and severity of the disease. In most cases, however, there are complaints in the area of the stomach and intestines. The skin can also be affected by changes. If the graft-versus-host reaction is not treated properly or not treated early, the patient may also die. Intestinal symptoms are usually caused by intestinal inflammation. This is associated with severe pain and diarrhea. Likewise, complete failure of the liver can occur, leading to death. Treatment only takes place if the graft-versus-host reaction represents a life-threatening condition for the patient. Medication is primarily used and no further complications occur. Treatment is closely monitored to prevent infections and inflammation. In severe cases, radiation may also be performed. Usually, life expectancy is not reduced by graft-versus-host reaction if its treatment is done properly. However, life expectancy may have already been reduced by the previous cancer.
When should you see a doctor?
In most cases, graft-versus-host reaction is diagnosed while the patient is still in the hospital and thus can be treated relatively quickly. For this reason, an additional diagnosis is no longer necessary. Treatment by a physician is necessary if symptoms occur in the stomach or intestines after a transplant. In this case, the affected person suffers from pain during bowel movements or abdominal pain in general. Frequently, diarrhea also indicates the graft-versus-host reaction and should be examined, especially after a transplant. The discomfort may also not occur until several weeks after the procedure. If the symptoms are noticeable, the doctor treating the transplant or a hospital should be consulted immediately. Treatment is then also usually carried out on an inpatient basis in order to avoid liver failure and thus the death of the patient. Whether a positive outcome will occur cannot generally be predicted. However, early diagnosis and treatment have a positive effect on the course of the disease.
Treatment and therapy
In principle, a graft-versus-host reaction to a mild extent is not necessarily life-threatening and may even benefit the recipient in cancer cases, killing the remaining cancer cells. Nevertheless, the reaction should not be left untreated or uncontrolled. Therapeutic measures against a graft-versus-host reaction consist of prophylaxis and actual treatment. Prophylaxis is given to every transplant recipient. It is intended to prevent the reaction and is started before the transplantation. The main drugs used for prophylaxis are ciclosporin A and methotrexate. Immunosuppressants such as corticosteroids, antimetabolites or monoclonal anti-lymphocyte antibodies are also standard prophylaxis in transplantation today and can prevent or at least control immunologically induced rejection in many cases. If the acute form of graft-versus-host reaction occurs despite extensive prophylaxis and a relatively compatible graft, corticosteroids are given in high doses in addition to standard immunosuppressants. If there is no improvement despite this treatment, the patient of the acute form receives TNF-α antibodies. To prevent the chronic form, platelet and granulocyte concentrates are prophylactically irradiated before transfusion, for example. If a reaction nevertheless develops, prednisolone or azathioprine are available as regulating drugs.
Outlook and prognosis
The prognosis of graft-versus-host reaction must be evaluated according to the individual circumstances and the health status of the affected person. In principle, organ transplantation carries a high risk for each patient. The mortality rate in the presence of a graft-versus-host reaction is approximately ten percent. Although a large number of patients do not experience any significant adverse effects as a result of transplantation, complications and functional disorders can occur at any time. If medical treatment is discontinued on the patient’s own responsibility, the mortality rate increases further. The prognosis is also tied to the severity of the disease present. If the severity is mild, the prospect of relief is favorable.The administration of medication is often sufficient for the situation to improve. In most cases, the patient can be discharged from treatment as symptom-free in the further course. However, regular check-ups are still necessary so that changes and abnormalities can be detected and treated as early as possible. If the donor organ is accepted by the organism with the help of drug treatment, the prognosis is favorable. Often time is needed for the changeover. If the body successfully overcomes the acclimatization processes, the patient’s life expectancy and quality of life increase considerably. In addition, measures that lead to attenuation of the graft-versus-host reaction can be taken advantage of in the run-up to transplantation.
Prevention
In the current state of medicine, graft-versus-host reaction in the setting of transplantation can be prevented to some extent by immunosuppressive prophylaxis and selection of relatively immunocompatible grafts. However, it is still not possible to exclude with certainty the corresponding reactions during transplantation despite medical progress and prophylactic measures today.
Aftercare
Aftercare in graft-versus-host reactions can often be avoided by appropriate prophylaxis. Here, the donor’s immune cells attack the recipient’s body, rather than the other way around. In addition to acute graft-versus-host reaction, there is a chronic variant that requires lifelong immunosuppression. Since this is a frequent sequela of allogeneic blood stem cell or bone marrow transplantation, a donor-versus-recipient reaction should be prevented from the outset. The therapy of an acute graft-versus-host reaction depends on its severity. If preventive measures have not been sufficiently successful, systemic immunosuppressive treatment with corticosteroids is initiated in case of a moderate to severe graft-versus-host reaction. Transplant patients require lifelong follow-up care anyway. This also applies to patients who have survived bone marrow or stem cell transplants. Often, the donor cells and the transplant patient’s genes are not a 100 percent match. A graft-versus-host reaction can occur due to individual circumstances despite all precautions. The patient’s age plays a role in follow-up or survival after a graft-versus-host reaction, as does his or her underlying disease. All follow-up concerns the underlying disease, which may be in various stages of treatment or in remission. Acute graft-versus-host reaction requires prompt acute treatment. Since it can occur in 30 to 60 percent of transplant cases, treating physicians are prepared for corresponding symptoms. They can take immediate action with the onset of this complication.
Here’s what you can do yourself
Graft-versus-host reaction – GVHR for short – is, in simple terms, the body’s own defense reaction against implanted cells. The diagnosis is made by a physician; GVHR cannot be diagnosed by the patient himself. However, the patient can contribute to an early detection of GVHR if he or she is able to provide information about his or her condition and state of health. GVHR is also treated by medical therapy. Self-help of the affected patient is not possible. In the majority of cases, patients undergoing organ or spinal cord transplantation are under intensive medical observation and are regularly tested for possible GVHR. Only in isolated cases does a GVHR develop at a later time, when the patient has already left the hospital. However, it is equally true for all transplanted patients that a healthy lifestyle strengthens the immune system and contributes to maintaining health. This includes completely abstaining from nicotine, alcohol or drugs. Coffee should only be consumed in small to moderate amounts, and excessive consumption of sugar and fat should also be avoided. A physical activity program in the fresh air, the intensity of which should be discussed with the doctor, can also help to improve the general condition.
