Graft Versus Host Disease (GVHD)

What is graft versus host disease?

Graft versus host disease (GVHD) is a condition that can happen after an allogeneic stem cell transplant (also called a bone marrow transplant). In GVHD, immune cells from the donor attack healthy tissues in the patient’s body.  

There are 2 kinds of transplants based on the source of the blood-forming stem cells: allogeneic and autologous. An allogeneic transplant occurs when the cells come from another person. An autologous transplant occurs when the cells come from the patient. GVHD occurs when donor immune cells (allogeneic) attack the patient’s normal cells by mistake.

GVHD symptoms depend on which parts of the body are affected, such as the skin, digestive tract, liver, eyes, and mouth. Based on symptoms and when they develop, GVHD may be considered acute GVHD or chronic GVHD.  

GVHD can be graded as mild, moderate, or severe. In some cases, GVHD can be life threatening. Your care team will take steps to help lower the risk of GVHD and plan follow-up care based on your child’s needs. Treatments for GVHD can help regulate the immune response, relieve symptoms, and prevent tissue and organ damage. 

Symptoms of GVHD

Acute GVHD

Acute GVHD most often affects the skin, gastrointestinal (GI) tract, and liver. It often occurs during the first 100 days after transplant, but can occur later.  

Signs and symptoms of acute GVHD (aGVHD) often appear and worsen quickly, and may include:

Skin

• Rash
• Redness
• Blisters
• Ulcers

GI tract

• Nausea or vomiting
• Loss of appetite
• Watery or bloody diarrhea
• Abdominal (belly) pain

Liver

• Jaundice or yellowing of the skin or whites of the eyes
• Changes in liver test results
• Liver problems

Chronic GVHD

Chronic GVHD can affect many organs. It is similar to an autoimmune disease because the donor cells continue to attack healthy tissues. Chronic GVHD often develops more than 100 days after transplant, but can happen earlier. 

Signs and symptoms of chronic GVHD (cGVHD) often appear and worsen slowly, and may include:

Skin, hair, and nails

• Skin rash, itching, dryness, or flaking
• Change in skin color
• Skin that feels thick, tight, or hard
• Hair thinning or hair loss
• Brittle, damaged, or missing nails

Mouth and digestive tract

• Dry mouth
• Mouth sores or pain  
• Trouble swallowing
• Sensitivity to hot, cold, spicy, or acidic foods
• Loss of appetite or weight loss 
• Nausea, vomiting, or diarrhea

Eyes

• Dry, red, painful, or irritated eyes
• Sensitivity to light
• Changes in vision

Lungs

• Cough
• Shortness of breath
• Wheezing
• Breathing problems during physical activity

Muscles and joints

• Joint stiffness or pain
• Skin tightness that limits movement
• Problems moving or doing usual activities

Liver

• Jaundice (yellowing of the skin or whites of the eyes)
• Changes in liver test results
• Dark urine

Genitals and sexual health

Chronic GVHD can affect the genital area in both females and males. Symptoms may include:

• Dryness, redness, itching, burning, or sores 
• Pain with sex or sexual activity 
• Skin changes, tightening, or scarring 
• Burning or discomfort with urination
• Lack of interest in sex

Risk factors for GVHD

Several factors can affect a person's risk of developing GVHD after an allogeneic stem cell transplant. Risk factors for GVHD include:

• How closely the donor matches your child
• Whether the donor is related or unrelated
• The age of the donor and recipient
• The source of the donor cells (bone marrow, peripheral blood stem cells, or cord blood)
• The type and intensity of treatment given before transplant
• Whether your child already had acute GVHD

Your child's care team considers these factors when choosing a donor and planning treatment.

Prevention of GVHD

Your child’s care team will take steps to help prevent GVHD. 

Donor selection 

Your child’s care team will choose the closest HLA-matched donor available. HLA stands for human leukocyte antigens. HLA are proteins or markers that are on most cells in the body. The immune system uses HLA to recognize which cells belong in your body and which ones don’t.

Each person has a different combination of HLA markers. They are determined by genes, which are inherited, or passed down from parents to children. So, family members may have similar HLA types. Since children inherit one set of HLA markers from each parent, parents are always a half match to their children. Each brother or sister who has the same parents has a 25% chance (1 in 4) of being a close HLA match. 

HLA typing is an important first step of testing before an allogeneic stem cell (bone marrow) transplant. The HLA type of your child should match that of the donor as much as possible. If the donor cells are not well-matched to your child's HLA type, your child's cells and the donor cells may attack each other.  

Even with a close match, GVHD can still occur.

Donor cell processing 

In some transplants, donor cells are processed to remove or reduce certain immune cells that increase the risk of GVHD.

Immunosuppressive medicines 

Your child may receive medicines that help reduce the activity of the donor's immune cells. Medicines to help lower the risk of GVHD may include:  

Depending on the transplant plan, the medicines may be given before, during, or after the transplant. Some are given by IV, and others are taken by mouth. Your child may take some medicines for several months. They may need regular blood tests to check medicine levels and help the care team adjust the dose if needed.  

Diagnosing and monitoring of GVHD

Your child will be checked closely for signs of GVHD after transplant.  This may include regular physical exams, monitoring symptoms, and lab tests.

Tests may include:

• Physical exams to look for changes in the skin, mouth, eyes, joints, and other parts of the body.  
• Blood tests to check liver function and monitor other changes that may be related to GVHD.  
• Imaging tests if your child has symptoms that affect certain organs.
• Biopsy, which involves removing a small sample of tissue to look for signs of GVHD. Depending on symptoms, this may include a skin biopsy or other tissue biopsy.
• Endoscopy or colonoscopy to look for GVHD in the digestive tract if your child has symptoms such as nausea, vomiting, belly pain, or diarrhea.

Treatment of GVHD

Treatment depends on the type and severity of GVHD and which parts of the body are affected. Chronic GVHD can last months or years and sometimes requires long-term treatment.

Medicines

Medicines may be given by vein, mouth, cream, ointment, eye drops, or mouth rinse, depending on your child’s symptoms. Treatment with medications often lasts for several months. 

Corticosteroids are often used to treat GVHD. Examples include methylprednisolone, dexamethasone, and prednisone. If steroid medicines do not control GVHD, other medicines that target the immune system may be used. Immunosuppressive medications are often used to help train the donor cells to keep them from causing further damage. 

Phototherapy

Some children may receive a light-based treatment for GVHD, called narrowband UVB phototherapy. It uses a type of ultraviolet light to treat skin problems caused by GVHD. Phototherapy is typically administered by a dermatologist (skin doctor) in close consultation with your transplant doctor.  

Extracorporeal photopheresis

During extracorporeal photopheresis (ECP), an apheresis machine separates the blood and removes white blood cells. The white blood cells are treated with medicine and ultraviolet light. The white blood cells are returned to your child’s body. The treated white blood cells help change how the immune system responds. This may help reduce the immune attack that causes GVHD.

ECP is typically used when GVHD does not improve with other treatments (refractory GVHD). It requires repeated visits, and patients often need a central line placed to receive ECP.  

Tips for families

It is not always possible to prevent GVHD. But following the care plan, watching for symptoms, and getting care early can help. 

• Give all medicines as directed. It is important that your child takes medicines exactly as prescribed. Do not stop, skip, or change a dose unless your care team tells you to do so. Let your care team know if your child has a problem taking any of their medicines.
• Watch for GVHD signs and symptoms. Tell your care team about any new or worsening symptoms right away. Check your child’s skin and pay attention to changes in eating, breathing, eyes, mouth, movement, and energy. Early care for GVHD is important for your child’s long-term health.
• Protect your child’s skin from the sun and follow recommendations for skin care. Sun exposure may trigger GVHD or make skin symptoms worse. Follow your care team’s instructions about sunscreen, protective clothing, and time outdoors. Ask your care team how to care for your child’s skin.
• Follow diet recommendations. Your care team may ask your child to follow a special GVHD diet that includes bland, easy-to-digest foods. GVHD can cause abdominal pain, nausea and vomiting, and diarrhea. Following a GVHD diet allows the digestive tract to heal.
• Take steps to prevent infection. GVHD and the medicines used to treat it can weaken the immune system. Help prevent infection by washing hands often, keeping areas clean, staying away from people who are sick, and getting recommended vaccines. Tell all health care providers about your child’s medical history. Contact your care team right away if your child develops a fever or other signs of infection.
• Keep all medical appointments. Your child will need regular follow-up care after transplant. These visits help the care team watch for signs of GVHD, monitor recovery, and manage any treatment side effects. GVHD can develop months after transplant, so ongoing monitoring is important. 

When to call your care team

Contact your child's care team right away if your child develops any new symptoms, symptoms that get worse, or symptoms that do not improve.

Also, tell your care team if your child has a fever or other signs of infection, trouble taking medicines, or any changes that concern you.

Questions to ask your care team

• What is my child’s risk of developing GVHD? 
• What symptoms of GVHD should I watch for? 
• What steps are taken to help prevent GVHD?
• Which medicines will my child receive to help manage GVHD? 
• How will my child be monitored for GVHD? 
• How can I protect my child’s skin from the sun? 
• Are there foods, products, or activities that my child should avoid? 
• How might GVHD affect my child’s daily activities or school? 
• What treatments may be needed if GVHD develops?
• What follow-up care will my child need? 

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