What is Graft Versus Host Disease & How is it Treated? | Causes, Symptoms, Diagnosis of Graft Versus Host Disease

Graft versus host disease is a serious and potentially life threatening medical conditions seen exclusively in people who undergo allogenic transplants. This form of transplant consists of using healthy cells from the donor and transplanted into the patient or the recipient. The classic example for a graft versus host disease can be seen in people with certain forms of cancer that undergo stem cell transplant along with radiation and chemotherapy as a form of treatment. The healthy cells of the donor, most commonly a sibling, and transplanted into the patient. These healthy cells then attack the cancer cells in the recipient and destroy them. This is also called as graft-versus-host effect.^[2]

However, sometimes, these donor cells start attacking and destroying the healthy cells in the recipient causing a variety of medical problems some of which are quite serious. This is what is termed as Graft-Versus-Host Disease. This condition is classified mainly into two types, acute and chronic.^[2]

Acute Graft-Versus-Host Disease: This occurs when the recipient’s body acts negatively towards the cells transplanted from the donor. Experts estimate that about 80% of cases of allogenic transplant patients’ end up having Acute Graft-Versus-Host Disease.^[2]

This condition is diagnosed normally within the first three months of the transplant, in fact the first two to three weeks to be precise following the transplant. Acute Graft-Versus-Host Disease can affect the skin, liver, and the stomach resulting in symptoms like rash, diarrhea, vomiting, and increase in liver enzymes.^[2]

Chronic Graft-Versus-Host Disease: This occurs in people who have acute form of this disease. Chronic Graft-Versus-Host Disease can be observed anywhere between 3 months to up to a year after the transplant procedure. The symptoms of this condition can range from mild to even severe which can render the patient literally disabled.^[2]

Chronic Graft-Versus-Host Disease can affect vital organs of the body like the liver and the lungs. It also affects the skin causing rashes, scaling of the skin, and skin discoloration. The joints may also get affected due to Graft-Versus-Host Disease where the mobility of the patient gets restricted. It also can cause irritation and redness of the eyes. There can be scarring of the lungs due to chronic Graft-Versus-Host Disease. It also can cause liver dysfunction and jaundice.^[2]

Graft-Versus-Host Disease is the body’s immune response to a foreign body, which in this case are the healthy cells of the recipient and not the donor cells which have been transplanted during an allogenic transplant. Technically speaking, the T cells of the donor which is actually white blood cells responsible for warding off infection do not recognize cells of the recipient in whichever organ they are transplanted.^[1,2]

Additionally, the allogenic transplant like the stem cell transplant causes damage to the tissues of the affected area. This releases inflammatory proteins. These proteins are responsible for stimulation of the protein cells. This further causes activation of the T cells which start attacking the recipient’s healthy cells. As the cells start to get destroyed by this process more intense immune response is triggered causing a variety of symptoms as those seen with Graft-Versus-Host Disease.^[1,2]

An allogenic transplant like the stem cell transplant can be successful without Graft-Versus-Host Disease when the HLA of the donor and recipient closely match each other. The human leukocyte antigen or the HLA is a unique protein that even individual inherits from each parent. The HLA of every individual is different, except in cases of identical twins when there is a complete match.^[1,2]

Thus physicians who do complex procedures like the stem cell transplant ensure that the HLA of both the donor and the recipient match as closely as possible to prevent post procedure complications like Graft-Versus-Host Disease. However, HLA matching is not 100% secure and the risk of Graft-Versus-Host Disease still remains. The risk of Graft-Versus-Host Disease increases if^[2]

• The recipient and donor are not blood relatives
• Complete HLA mismatch
• Excess T cell count in the stem cells of the donor
• The more the age of the donor the higher the risk
• The donor has been infected with infections like cytomegalovirus^[2]

In cases of acute Graft-Versus-Host Disease, there will be a typical skin rash detected especially in the palms of the hands, soles of the feet, face, and ears. There may also be pain and itching around the affected area.^[2]

Other symptoms of Graft-Versus-Host Disease include skin erythema, diarrhea with nausea and vomiting, stomach cramping, poor appetite, intestinal bleeding, jaundice indicating liver damage, ulcers in the mouth and throat, trouble breathing, unintentional weight loss, restricted joint motion, hair loss, redness and irritation of the eyes, and excess fatigue.^[2] For any person who has received a stem cell transplant and has any of these symptoms should consult with the physician immediately for treatment.

The symptoms of the patient after the transplant in most cases confirm the diagnosis of Graft-Versus-Host Disease. Additionally, a tissue biopsy is also done for confirmation of the diagnosis. Common sites from where the tissue sample for biopsy is taken include skin, liver, stomach, and intestine.^[1,2]

The frontline treatment for Graft-Versus-Host Disease includes medications to suppress the immune system along with nonsteroidal antiinflammatory drugs or steroids. The choice of medication depends on whether the patient has acute or chronic Graft-Versus-Host Disease. The duration of treatment may go on for at least a year and more depending on the responsiveness of the patient to treatment modalities.^[2]

Some of the medications used for treatment of acute Graft-Versus-Host Disease include glucocorticoids and cyclosporine. Some of the newly added medications include antithymocyte globulin, Ontak, Zenapax, and Remicade. CellCept is also quite effective in treating acute Graft-Versus-Host Disease. Chronic Graft-Versus-Host Disease is generally treated with medications that include Zenapax, Enbrel, Remicade, and CellCept.^[2]

In summary, Graft-Versus-Host Disease is quite a serious and potentially life-threatening medical condition that occurs in people who undergo allogenic transplant such as stem cell transplant for treatment of certain forms of cancer. In this condition, the immune cells start attacking the healthy cells of the body of the recipient causing severe damage to various organs including liver and lungs.^[1,2]

The severity of the condition varies from mild to severe. The prognosis of Graft-Versus-Host Disease depends on the severity of the condition and the overall health status of the patient. Thus it is recommended for people who have undergone stem cell transplant and they have any of the symptoms outlined above then they should seek immediate consultation with a physician to rule out or get treated for Graft-Versus-Host Disease.^[1,2]

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