Graft-versus-host Disease Definition and Meaning

Graft-versus-host Disease Definition and Meaning

According to DIGOPAUL, graft -versus-host disease is an immunological complication that can lead to graft rejection in allogeneic transplantation. The reaction can now be controlled by the prophylactic administration of immunosuppressants. Despite this, the mortality rate is still ten percent today.

What is Graft versus Host Disease?

In a transplant, organic material is transplanted from a donor into a recipient. When the donor and recipient are not twins, it is an allogeneic transplant. The tissue of the recipient is not genetically identical to the tissue of the donor. Therefore, rejection can occur. Graft-versus-host disease is often present in such cases. In fact, this reaction is one of the most common complications of transplants.

It is a cytotoxic immunological reaction that the implanted or transfused immune cells in the transplant undertake against the recipient’s organism. Especially the T-lymphocytes react against the transplant recipient. The literal translation of graft versus host disease is graft versus host disease. It plays a role above all in bone marrow transplants and stem cell therapies, but is also observed in other transplants. There are four different degrees of severity of the reaction.

Causes

Graft-versus-host disease is caused by the engraftment of foreign immune cells. Immunological 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 of a complication such as graft-versus-host disease depends on the immunological compatibility of the recipient and donor organism. The human leukocyte antigen determines this compatibility and should be the same if possible. However, even when transplanted from sibling donors with the same HLA, mild to moderate graft-versus-host disease develops in over a third of the cases.

The stability of the recipient organism also influences the risk of reaction. Recipients with a healthy immune system usually break down the transferred immune cells without complications. Immunocompromised hosts are unable to do this.

Symptoms, Ailments & Signs

Graft-versus-host disease symptoms depend on the severity. In people with a weakened immune system, serious diseases such as atrophy of the lymphatic organs, disorders of the gastrointestinal tract and skin changes or cachexia are conceivable. Graft-versus-host disease can even be fatal. A reaction in the first few weeks after a transplant is referred to as an acute graft-versus-host disease.

The epithelial cells of the skin are affected by maculopapular exanthema or erythroderma. In the intestines, intestinal inflammation enteritis often occurs with consequences such as diarrhea or painful bowel movements tenesmus. The liver reacts at the same time with jaundice, which can lead to liver failure. Chronic graft-versus-host disease only sets in after about three months.

Severe infections and mucosal changes in the gastrointestinal tract are its main symptoms. In addition, the serous membranes of the skin and liver can be affected. In all forms, the reaction manifests itself primarily in symptoms of the skin, liver, intestines or eyes.

Diagnosis & History

The acute form of the graft-versus-host reaction manifests itself histologically in a lymphocytic infiltration. Cell damage and cell death are also present. The histological proof of these circumstances has diagnostic value after a transplantation.

Since the symptoms are relatively typical and are directly related to a transplant, the diagnosis is relatively simple. The course depends on the severity of the reaction.

Although the current state of medicine has ways of significantly reducing the risks of graft-versus-host disease, the mortality rate from immunological rejection for allogeneic transplants is currently still around ten percent.

Complications

Graft-versus-host disease can cause a variety of complications and symptoms. However, the further course depends on the extent and severity of the disease. In most cases, however, there are problems in the stomach and intestines. The skin can also be affected by changes.

If the graft-versus-host disease is not treated properly or early, it can also lead to the death of the patient. Intestinal complaints are usually caused by intestinal inflammation. This is associated with severe pain and diarrhea. It can also lead to complete liver failure, resulting in death.

Treatment is given only when graft-versus-host disease is a life-threatening condition for the patient. Mostly drugs are used and there are no further complications. The treatment is closely monitored to prevent infections and inflammation.

Radiation can also be used in severe cases. Graft-versus-host disease does not usually reduce life expectancy if its management is properly managed. However, life expectancy may have been reduced by previous cancer.

When should you go to the doctor?

In most cases, graft-versus-host disease is diagnosed in the hospital and can therefore be treated relatively quickly. For this reason, an additional diagnosis is no longer necessary. Treatment by a doctor is necessary if there are problems in the stomach or intestines after a transplant.

Those affected suffer from pain during bowel movements or abdominal pain in general. Diarrhea is also often a sign of graft-versus-host disease and should be checked, especially after a transplant.

The symptoms can also only appear a few weeks after the procedure. If the symptoms are noticeable, the doctor treating the transplant or a hospital must be consulted immediately. The treatment is then usually inpatient, in order to avoid liver failure and thus the death of the person concerned.

It cannot generally be predicted whether a positive course will occur. However, early diagnosis and treatment has a positive effect on the course of the disease.

Treatment & Therapy

Basically, a mild degree of graft-versus-host disease is not necessarily life-threatening, but can even benefit the recipient in the case of cancer and kill the remaining cancer cells. Nevertheless, the reaction must not take place untreated or uncontrolled.

The therapeutic measures against a graft-versus-host reaction consist of prophylaxis and actual treatment. Every transplant recipient receives prophylaxis. It is intended to prevent the reaction and is started before the transplant.

Drugs such as ciclosporin A and methotrexate are primarily used for prevention. Immunosuppressive drugs such as corticosteroids, antimetabolites or monoclonal antilymphocyte antibodies are now part of the standard of prophylaxis in transplantation and can in many cases prevent or at least control immunologically induced rejection.

If, despite extensive prophylaxis and a relatively compatible transplant, the acute form of the graft-versus-host reaction occurs, corticosteroids are given in high doses in addition to the standardized immunosuppressants.

If there is no improvement despite this treatment, the patient in the acute form receives TNF-α antibodies. In order to prevent the chronic form, platelet and granulocyte concentrates are, for example, prophylactically irradiated before the transfusion. If a reaction occurs anyway, prednisolone or azathioprine are available as regulating drugs.

Outlook & Forecast

The prognosis of the graft-versus-host disease has to be evaluated according to the individual circumstances and the state of health of the affected person. Basically, the transplantation of an organ involves a high risk for every patient.

The mortality rate is about 10% when there is a graft-versus-host disease. Although a large number of patients do not experience any significant impairments from a transplant, complications and functional disorders can occur at any time.

If medical treatment is discontinued by the person concerned, the mortality rate increases further. The prognosis is also linked to the severity of the present disease. If the extent is weak, the prospect of alleviating the symptoms is good.

The administration of medication is often sufficient to improve the situation. In most cases, the patient can be discharged from the treatment as symptom-free. However, regular check-ups are still necessary so that changes and abnormalities can be recognized 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. Time is often required for the changeover. If the body successfully overcomes the habituation processes, the life expectancy and the quality of life of the patient increase significantly. In addition, measures can be taken in the run-up to the transplantation that lead to a weakening of the graft-versus-host reaction.

Prevention

With the current state of medicine, graft-versus-host disease in transplantation can be prevented to a certain extent by immunosuppressive prophylaxis and the selection of relatively immunocompatible transplants. However, despite medical progress and prophylactic measures, the corresponding reactions in a transplant cannot be ruled out with certainty.

Aftercare

Follow-up care for graft-versus-host reactions can often be avoided by appropriate prophylaxis. Here, the donor’s immune cells attack the recipient’s body, not the other way around. In addition to acute graft-versus-host disease, there is a chronic variant that requires lifelong immunosuppression.

Since it is a common consequence of allogeneic blood stem cell or bone marrow transplantation, a donor-versus-recipient reaction should be prevented from the outset. The treatment of an acute graft-versus-host reaction depends on its severity.

If preventive measures have not been sufficiently effective, systemic immunosuppressive treatment with corticosteroids is initiated for moderate to severe graft-versus-host disease. 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 genes of the transplant patient do not match 100 percent. A graft-versus-host reaction can develop due to individual circumstances despite all precautionary measures. The age of the patient plays a role in follow-up care or the chances of survival after a graft-versus-host disease, as does his underlying disease.

All follow-up measures concern the underlying disease, which can be in different stages of treatment or in remission. Acute graft-versus-host disease requires immediate acute treatment. Since it can occur in 30 to 60 percent of transplant cases, the treating physicians are prepared for the corresponding symptoms. You can take immediate action when this complication occurs.

You can do that yourself

Put simply, the graft-versus-host reaction – GVHR for short – is an endogenous defense reaction against implanted cells. The diagnosis is made by a doctor, GVHR cannot be diagnosed by the patient himself. However, if the patient is able to provide information about his condition and how he is feeling, he can contribute to the early detection of GVHR.

GVHR is also treated with medical therapy. It is not possible for the affected patient to help himself. In the majority of cases, patients after organ or spinal cord transplantation are under intensive care medical observation and are regularly tested for possible GVHR. Only in isolated cases does GVHR develop at a later point in time, when the patient has already left the hospital.

For all transplant patients, however, it is equally true that a healthy lifestyle strengthens the immune system and contributes to maintaining health. This includes the complete renunciation of nicotine, alcohol or drugs. Coffee should only be consumed in small to medium amounts, and excessive consumption of sugar and fat should also be avoided. A physical exercise program in the fresh air, the intensity of which should be discussed with the doctor, can also help to improve your general condition.

Graft-versus-host Disease