Graft vs. Host Disease (GVHD): Symptoms, Treatment, and More

Graft vs. host disease (GVHD) can occur after a stem cell transplant from a donor. Transplants replace unhealthy cells with healthy blood-forming cells, which can treat some cancers.

GVHD happens when the transplanted cells recognize your body’s cells as foreign and attack them.

GVHD may be acute (short-term) or chronic (long-term). Depending on what organs it affects, GVHD can lead to many symptoms.

There are two main types of GVHD, categorized based on when symptoms begin. Healthcare providers sometimes use other classifications.

Acute GVHD

Acute GVHD typically develops within the first 100 days of transplantation, but it can develop later in some cases. It affects the skin, gastrointestinal tract, and liver. About 30-70% of people receiving a transplant develop acute GVHD.

Chronic GVHD

Chronic GVHD can develop at any time following the transplantation, but it usually occurs more than 100 days after. Chronic GVHD can affect a single organ or multiple organs. About 40-50% of people undergoing transplantation may develop chronic GVHD.

Other Classifications

Healthcare providers sometimes describe GVHD in other ways. These include:

• Persistent, recurrent, or late-onset acute GVHD: This type has characteristics similar to acute GVHD but develops more than 100 days after transplantation.
• Overlap syndrome: This type can develop any time after you receive a transplant and has features of both acute and chronic GVHD.

Symptoms of graft vs. host disease can vary depending on the type of GVHD and the organs affected. Some of these symptoms may be mild, while others can be severe or life-threatening.

Acute GVHD symptoms

Acute GVHD most often affects the skin, digestive tract, and liver.

Skin symptoms: A sunburn-like rash may appear on any part of your skin. The rash may be slightly itchy at first, but it can become more severe and cause blisters or skin peeling.

Digestive symptoms: The most common digestive symptom is severe diarrhea. Other digestive symptoms include:

• Nausea
• Pain in your abdomen
• Vomiting
• Loss of appetite
• Blood in stool

Liver symptoms: Liver problems associated with GVHD don’t normally cause symptoms and can only be detected through liver function tests. However, severe liver damage can lead to symptoms such as:

• Jaundice (yellowing of the skin and whites of the eyes)
• Ascites (fluid buildup in the abdomen)
• Mental confusion

Chronic GVHD

Chronic GVHD can affect multiple organs, which can lead to many symptoms. These include:

• Dry mouth, painful mouth sores, tooth decay, and difficulty eating and swallowing
• Blurred vision
• Itchy and thickened skin
• Hair loss on your head and body
• Nausea, vomiting, diarrhea, and loss of appetite
• Shortness of breath
• Muscle weakness and cramps
• Joint stiffness 
• Itchy genitals and painful intercourse

When you receive a stem cell transplant, your body develops new immune cells from the donor’s stem cells. If these new immune cells mistake your own cells as foreign, it can trigger an immune response against your body.

This immune response can occur because your immune system is trained to distinguish between its own cells and foreign cells. Your immune system does this by recognizing proteins called human leukocyte antigens (HLAs) that are on the surface of most cells in your body.

Your body’s HLA markers are unique to you. Unless your donor is a twin, their HLA markers will be different from yours.

Before a stem cell transplant, healthcare providers check your cells’ compatibility with the donor cells. They do this with HLA typing, also called a tissue typing test, which helps them see how similar your HLA markers are.

Despite this testing, the new immune cells sometimes find your HLA to be too different from their own, which can trigger an immune response.

Risk Factors

Some factors may make GVHD more likely after receiving a transplant. These include:

• Stem cells from a related donor with an HLA mismatch
• Stem cells from an unrelated donor with an HLA mismatch
• Older age (for you or the donor)
• A male recipient receiving the transplant from a female donor (especially if she has been pregnant before)
• A previous diagnosis of acute GVHD

There is no specific test to diagnose graft vs. host disease. Instead, a healthcare provider may diagnose this condition based on your symptoms and different test results.

Your provider will likely do a physical exam and recommend tests to rule out other conditions that cause similar symptoms, such as infection or liver disease.

The treatment of GVHD depends on factors such as your overall health, the severity of the GVHD, and the affected organs. In cases where symptoms are more severe, you may need to be treated in a hospital.

Healthcare providers often treat GVHD with immunosuppressant treatments, which are drugs or procedures that reduce the immune response. If those don’t work well, they may use other medications.

Immunosuppresant Treatments

Treatments that may help reduce symptoms by decreasing your immune response include:

• Corticosteroids: Steroid medications such as Medrol (methylprednisolone) and Deltasone (prednisone) are a go-to treatment to help suppress your body’s immune activity and reduce inflammation. Topical corticosteroids or moisturizers may help GVHD that affects your skin.
• Calcineurin inhibitors: Your healthcare provider may prescribe medications such as Prograf (tacrolimus) and cyclosporine, along with steroids, to suppress your immune system.
• Biologics: Biologics, such as interleukin-2 (IL-2) receptor antibodies and tumor necrosis factor (TNF) inhibitors, may help reduce inflammation and symptoms by targeting specific proteins or cells in the immune system.
• Antithymocyte globulin: These drugs help suppress the immune system in severe cases that do not respond to other treatment options.
• Photopheresis: This procedure involves removing white blood cells from your blood, treating them with ultraviolet light, and returning them to your body. This process can reduce the immune response and is most often used for people with chronic GVHD.

Other Treatments

The United States Food and Drug Administration (FDA) has also approved several other drugs for the treatment of GVHD. These include:

• Imbruvica (ibrutinib): This oral medication may help treat chronic GVHD in adults after one or more traditional treatment approaches have not worked.
• Niktimvo (axatilimab-csfr): This infused drug may help treat chronic GVHD in adults and children after the failure of at least two previous treatments.
• Ryoncil (remestemcel-L-rknd): This infused treatment is for acute GVHD in children aged 2 months or older.
• Rezurock (belumosudil): This oral medication may help treat chronic GVHD in adults and children over 12 years old, after two or more previous treatments have not worked.

Your healthcare provider can help prevent GVHD by ensuring that your donor’s HLA markers closely match yours. The more markers you and the donor share, the lower the chance that your new immune cells from the donor will attack your healthy cells.

Your provider may also recommend immunosuppressive medications before and after the transplant to help prevent GVHD. Orencia (abatacept) is an FDA-approved medication to help prevent acute GVHD.

GVHD can sometimes lead to serious complications. These may include:

• Infections: GVHD or its treatment can increase the risk of bacterial, viral, and fungal infections.
• Interstitial lung disease: This is a group of lung disorders that cause scarring and inflammation in your lungs.
• Bronchiolitis obliterans syndrome (popcorn lung): This rare lung disorder occurs when the bronchioles (the small airways in the lungs) become narrow and scarred, which can lead to respiratory failure.
• Malabsorption: This condition occurs when your body is unable to absorb nutrients from food.
• Abnormal motility: With this disorder, the nerves or muscles in your intestinal tract do not work properly, leading to intestinal obstruction.

How graft vs. host disease affects your life may depend on how severe it is and what symptoms you experience. Early diagnosis and treatment are essential to prevent GVHD from becoming severe.

If you notice any unusual symptoms after receiving a transplant, contact a healthcare provider. They can diagnose and treat your GVHD.