What is Graft Versus Host Disease (GVHD)?

Graft Versus Host Disease (GVHD) is a common complication in patients who have had an allogeneic (donor) stem cell transplant. It occurs in 20% to 50% of all stem cell transplant recipients to some degree. Most cases are mild. However, it can also lead to severe and life-threatening complications.
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Allogeneic stem cell transplantation offers an effective treatment for blood cancers, including lymphoma and leukaemia.
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During allogeneic stem cell transplantation, the patient receives healthy stem cells from a donor. The healthy stem cells replace the cells in the bone marrow that generate the blood cells, including the white blood cells that form a part of the immune system.
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The aim of the transplant is to allow the donor stem cells to settle and grow (engraft) in the patient’s bone marrow. This allows the patient to produce new healthy donor blood cells.
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However, sometimes, the graft or the donor cells may proliferate too aggressively and attack the host cells in the patient’s body. This condition is referred to as “graft-versus-host disease” or GVHD.
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There are two main categories of GVHD, which are acute GVHD and chronic GVHD.
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Each type of GVHD may affect different tissues and organs, producing various symptoms. Patients may be diagnosed with one or both acute and chronic GVHD. In some patients, chronic GVHD may occur after acute GVHD, or both may occur concurrently.
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GVHD can be mild, moderate, or severe. In some cases, GVHD may not occur.
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What is Acute GVHD?

Acute GVHD usually begins within 100 days of the transplant. The frequency of acute GVHD varies significantly between populations making it difficult to determine how common it is.
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Acute GVHD primarily affects the skin, liver, and the gastrointestinal system (stomach, intestines and colon).
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What are the risk factors of Acute GVHD?

The following factors are associated with a higher risk of developing acute GVHD:

• HLA (human leukocyte antigen) “mismatch” or unrelated donor
• Older recipients
• Female donor to a male recipient
• The intensity of the total body irradiation and conditioning regimen
• Donor lymphocyte infusion, a procedure performed after stem cell transplantation that infuses more lymphocytes from donor stem cells
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A low blood count is not necessarily a sign of acute GVHD. However, it is prevalent for patients with GVHD to develop low blood counts.
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Patients should inform our doctors if they experience any of these symptoms. Timely detection and treatment may reduce the severity of the disease.
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What is Chronic GVHD?

Chronic GVHD begins more than 100 days after a transplant and may involve one or more organs. It may last for several years or even the lifetime of the patient. Chronic GVHD symptoms range from being mild to severe and even life-threatening.
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What are the risk factors of Chronic GVHD?

The following factors are linked to the risk of chronic GVHD:

• HLA mismatch or unrelated donor
• Older recipients
• Older donors
• A female donor and a male recipient
• The number of pregnancies a female donor has had.
• Prior acute GVHD
  

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Contact our doctors if any of these signs occur. Timely detection and treatment helps reduce the severity of this disease.
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How is GVHD treated with medication?

Different combinations of medications are used to treat this condition. Commonly used medications to prevent GVHD include:

• Methotrexate
• Cyclosporine
• Tacrolimus
• Mycophenolate mofetil
• Corticosteroids (prednisolone or methylprednisolone)
• Antithymocyte globulin (ATG)
• Alemtuzumab
• Cyclophosphamide
  

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What are the treatment options for GVHD?

Immunosuppression with steroidal drugs forms the basis of treatment for acute and chronic GVHD.
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Immunosuppression refers to the suppression of the immune system and the body’s ability to fight organisms or other disease-causing agents.
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Other drugs that control the immune response may also be used. Treatment may be either as an outpatient or inpatient. The choice of treatment and medicines used depend on the severity of the symptoms and the risk of complications.
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Treatment for Acute GVHD

After transplantation, patients continue the use of immunosuppressive drugs which are commenced before the transplant (such as cyclosporine, tacrolimus, and mycophenolate).
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Increased immunosuppression with corticosteroids is a typical treatment for patients with acute GVHD. Corticosteroids include medicines such as prednisolone, methylprednisolone and dexamethasone.
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In patients with systemic manifestations and/or more severe acute GVHD, primary immunosuppressives are continued, and a corticosteroid is usually added.
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Treatment for Chronic GVHD

Patients with mild symptoms affecting only a single site or organ can usually be managed through close monitoring or local therapies. For example, mild symptoms of the skin can be managed by using topical steroid ointments, and patients with GVHD affecting the eye can be treated with steroid eye drops.
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Patients must continue taking their medications even after the symptoms have resolved. Stopping the medicines too soon may cause chronic GVHD to flare up or worsen, which may result in permanent damage.
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Once chronic GVHD begins to stabilise and improve, doctors may consider tapering the medications over time, and eventually, the drugs may be discontinued.
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Side Effects of Treatment

Medications used to treat GVHD include immunosuppressants that work by weakening the immune system. Therefore, they may increase the patient’s risk of getting infections.
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In addition to infections, GVHD treatment may cause other side effects such as:

• Corticosteroids (prednisolone, methylprednisolone, dexamethasone, beclomethasone, clobetasol) – prolonged systemic use may cause weight gain, bone loss (osteoporosis), high blood sugar, high blood pressure, cataract formation, insomnia, mood swings, and depression.
• Cyclosporine/Tacrolimus may cause kidney problems and increased hair growth on the body. Additionally, while rare, they can also cause neurological issues such as seizures, tremors, confusion and anxiety.
• Methotrexate may cause liver problems, nausea, vomiting, abdominal pain, and mouth sores.
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Patients should inform our doctors if they develop these side effects. Our doctors will try to adjust the doses of medications to control the symptoms of GVHD while minimising the side effects. These side effects usually subside once treatment is stopped.
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Effective ways to prevent the complications of GVHD

The following are some suggestions to limit the complications of GVHD:

• If a doctor prescribes medications to prevent GVHD, it is essential to take these medications, even when patients are feeling healthy. If the patient is unable to take these medications, or if the symptoms of GVHD occur, contact our doctors immediately as timely detection and treatment can limit the extent of the disease.
• Patients need to try to prevent infections. Patients should wash their hands frequently and ask family members and friends who are sick not to visit them until they are healthy.
• Exposure to the ultraviolet rays in the sunlight may increase the risk of GVHD. It is important to avoid or minimise exposure to the sun. When outside, wear a hat, and long-sleeved clothes and pants. Some companies offer sun-protective clothing that can help shield the skin from the sun’s harmful ultraviolet rays. Apply sunscreen of SPF 30 or higher on the skin.
• Keeping the skin moist or well-hydrated can prevent it from getting dry or flaky. Avoid long showers and use a mild soap and a moisturising lotion every day. Try to avoid scratching. Our doctors may prescribe topical steroids such as creams to relieve itching and burning and to manage GVHD of the skin.
• Patients with chronic GVHD affecting the eyes should wear sunglasses with UV protection when outside to protect the eyes from further damage. You may be referred to an ophthalmologist for further management.
• Patients with chronic GVHD affecting the mouth tend to have a dry mouth, which can lead to cavities. Patients should maintain good oral hygiene. It is essential to see a dentist for routine dental cleanings and check-ups. Dental check-ups should be done 2 to 4 times per year for the prevention and maintenance of oral health issues.
• Patients with diarrhoea should follow the diet prescribed by our doctors and dietitian to prevent the worsening of symptoms. Avoid spicy foods. Diarrhoea may also cause skin problems and irritation around the rectal area. Clean this area well after each bout of diarrhoea. Inform our doctors should the area become red, cracked, painful, or infected.
• Regular exercise such as stretching will help to preserve bone health, decrease pain and fatigue, increase muscle strength, and improve mobility. Physiotherapy can help to improve joint strength and mobility and prevent disabilities that might occur as a result of chronic GVHD and the use of immunosuppressive treatments.
• Vaccinations will be recommended by our transplant team unless you are allergic to them. The immunity to diseases that patients acquired before their transplantation is generally lost after stem cell transplantation. Hence, our transplant centre starts to give vaccinations 6 – 12 months after transplantation. Vaccinations usually include DTaP, pneumococcal vaccine, inactivated flu vaccine, and hepatitis B. It is advised that patients with T-cell depleted transplantation or chronic GVHD avoid vaccinations made from live viruses (such as varicella – chickenpox) until the GVHD is resolved, and the use of immunosuppressive drugs has completed.
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Disclaimer:
The information on the Centre For Clinical Haematology website is intended for educational use.  It should not be considered or used as a substitute for medical advice, diagnosis or treatment from a qualified health professional.