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What Is Graft-Versus-Host Disease (GVHD)?

Posted on April 29, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Maureen McNulty

Several different types of cancers — including leukemia — can be treated with an allogeneic stem cell transplant. During this procedure, a person receives new blood cells from a donor. Graft-versus-host disease (GVHD) is a condition that may develop in a person who undergoes a stem cell transplant. In GVHD, the donated cells see the recipient’s body cells as foreign and attack them. GVHD can be life-threatening or low-grade. Treatments are available that can help keep GVHD under control.

What Is a Stem Cell Transplant?

Many cancer treatments can damage or kill not only cancer cells — but also normal, healthy cells. In particular, cancer treatments can destroy mature blood cells as well as blood stem cells. Stem cells live in the bone marrow (spongy tissue inside certain bones). Their job is to make new blood cells.

Stem cell transplants — sometimes called bone marrow transplants — are used to treat several different types of blood cancer. Before a stem cell transplant, a person with leukemia receives high-dose chemotherapy and sometimes radiation therapy. This aggressive treatment is more likely to kill cancer cells, but it is also designed to kill normal stem cells, leaving them unable to replace the damaged blood cells. In this way, stem cells can be infused back while the cancer cells may never recover.

After receiving aggressive treatments, a person with leukemia can undergo stem cell transplantation. There are two main types: autologous and allogeneic. During an autologous transplantation, a person’s own stem cells are taken out, treated, and then put back after high-dose chemotherapy. For the allogeneic type, a person receives new stem cells from a healthy donor.

Because stem cell transplantation involves aggressive treatments, it is not a good fit for everyone. For people who are older or have other health problems, the risks — including GVHD — may outweigh the benefits. Some people who can’t go through a full transplantation may be able to try a reduced-intensity allogeneic stem cell transplant, also called a mini-transplant. This procedure uses less aggressive chemotherapy and radiation. However, it may still occasionally lead to GVHD.

What Causes GVHD?

Graft-versus-host disease is one example of a complication that can occur after stem cell transplantation. A complication is a health condition that develops during a disease or following a treatment. GVHD can also occur after other procedures, including transplantation of an organ or blood transfusions — especially in immunocompromised people — although this is less common.

GVHD occurs because of an immune system reaction. Your healthy T cells are responsible for attacking foreign substances, like bacteria or viruses, that enter your body. However, T cells “know” not to attack your body’s own cells. This is because all of your cells have proteins called human leukocyte antigens (HLA) on their surfaces. Each person has unique HLA proteins — your HLA proteins are the same across all of your cells, but they are different from the ones found on anyone else’s cells.

During an allogeneic transplant, you get new stem cells from a donor. These stem cells eventually make new T cells. However, the new T cells have the same HLA proteins as the donor, which look a bit different than your own HLA proteins. The new T cells think that your body’s cells are foreign cells, and they attack. This leads to a range of different symptoms and health problems.

Your chances of being diagnosed with GVHD after an allogeneic stem cell transplant depend on how close of a match your donor is. You have a 35 percent to 45 percent chance of developing GVHD if you are related to your donor. If you are not related to the donor, your chance of developing GVHD is 60 percent to 80 percent.

Graft-versus-host disease is very rare after an autologous transplantation.

GVHD Risk Factors

Some people have HLA proteins that look more similar to your own. These donors are a better match, and receiving their cells will give you a lower chance of developing GVHD. Having a donor that is related to you, who is a very close HLA match, decreases your risk of GVHD.

Other risk factors may increase your chances of developing GVHD:

  • There are a lot of T cells in the donated stem cells.
  • You or your donor are older adults.
  • You and your donor have a different biological sex.
  • Your donor is infected with cytomegalovirus, but you are not.
  • You undergo a treatment called donor lymphocyte infusion, in which you receive some white blood cells from your donor.

Your doctor can help you better understand your own risk factors. If you are considering undergoing a stem cell transplant, ask your doctor about the risks and benefits you can expect.

Acute vs. Chronic GVHD

There are two different forms of graft-versus-host disease: acute and chronic. Acute GVHD appears soon after a transplant — within a few weeks or months. If GVHD develops more than three months after a transplant, doctors may call it “late acute GVHD.” Chronic GVHD takes longer to develop, but generally appears within a year of getting a transplant. In some cases, a person has overlap chronic GVHD, in which signs of both acute and chronic GVHD appear at the same time.

Mild, chronic GVHD can actually be beneficial. If your donated T cells are just a little active, they may not attack the healthy cells in your body — but they will aggressively attack your remaining cancer cells. This is known as the graft-versus-disease effect or graft-versus-leukemia effect. People who experience this effect are less likely to have a relapse (have their leukemia come back).

Symptoms of Graft-Versus-Host Disease

GVHD can cause a wide range of symptoms. These symptoms vary depending on whether a person has acute or chronic GVHD and on which type of body cell is attacked more. If you have acute GVHD, you may experience:

  • Abdominal pain
  • Nausea or vomiting
  • Diarrhea
  • Redness, itching, or a rash on the skin
  • Jaundice (yellowing of the skin or eyes)
  • Frequent infections

People with chronic GVHD can experience:

  • Dry or burning eyes
  • Changes in vision
  • Feeling of dryness in the mouth
  • White patches in the mouth
  • Sensitivity to spicy foods
  • Skin rash or areas of thick skin
  • Changes in sweating
  • Brittle or gray hair
  • Painful or stiff joints
  • Breathing difficulties
  • Weight loss

While you may notice different GVHD symptoms, lab tests may uncover additional signs. Tests may show that the liver isn’t making as much bile, a chemical that helps with digestion. They may also indicate cytopenia (low levels of blood cells). Heart tests can identify pericarditis (swelling around the heart).

In some cases, graft-versus-host disease can cause long-term problems. Some people with GVHD are left with damage to organs like the liver, lungs, or digestive system.

Diagnosing and Following GVHD

If you undergo stem cell transplantation, your doctor will monitor you with different tests. These tests may help your doctor determine whether you have GVHD or ensure that your GVHD is under control.

Tests may include:

  • Imaging tests, such as a CT scan, positron emission tomography (or PET) scan, X-ray, or MRI
  • Blood tests that measure how well your liver is working
  • Liver biopsy (removal of a small piece of liver tissue)
  • Biopsy of the skin or mouth
  • Capsule endoscopy (a procedure in which you swallow a pill that contains a camera, which takes pictures of your small intestine)

Treatments for GVHD

Graft-versus-host disease treatments may vary based on a person’s symptoms and type of GVHD. Diagnosing and treating the condition early can help stop GVHD from becoming too severe.

Acute GVHD Treatments

Acute graft-versus-host disease is often treated with immunosuppressants (medications that reduce the activity of the immune system). Many immunosuppressants are corticosteroids. These can include:

  • Decadron (dexamethasone)
  • Deltasone (prednisone)
  • Medrol (methylprednisolone)
  • Pulmicort (budesonide)
  • Qvar (beclomethasone)

Some people only have GVHD symptoms in the skin. These symptoms may be treated with a topical (applied directly to the skin) steroid, or with a medication like Gengraf (cyclosporine) or Protopic (tacrolimus).

Occasionally, a person with GVHD may develop resistance to steroids, meaning that the steroids no longer work. In these cases, a person may be able to take Jakafi (ruxolitinib). Ruxolitinib blocks proteins that cause inflammation and tissue damage during GVHD. Alternatively, steroid-resistant cases of GVHD may be treated with extracorporeal photopheresis (or ECP). During this treatment, a person’s white blood cells are removed, treated with light, and then returned to the body.

Chronic GVHD Treatments

Mild cases of chronic graft-versus-host disease may not need any treatments. People with skin symptoms can be treated with topical steroids, and people with eye symptoms can use eye drops that contain immunosuppressant drugs.

More severe cases of chronic GVHD are usually treated first with prednisone. If this steroid doesn’t reduce symptoms, then a person with GVHD may be able to take other immunosuppressants. Imbruvica (ibrutinib) may also help. This drug blocks immune cells that are involved in GVHD.

Long-term immunosuppression makes your immune system less effective, so these treatments make a person more likely to get infections. If your doctor prescribes you immunosuppressant medications, they will also probably give you other treatments that help prevent infections.

GVHD Outlook

People with GVHD have a wide variety of outcomes. Some cases of GVHD are mild, while others are life-threatening. In recent years, treatment options have improved survival for people with GVHD. Those who have mild cases of GVHD often have good outcomes. However, severe GVHD can lead to worse survival rates. One recent study found that 55 percent of people with severe acute GVHD live at least two years and that 74 percent of people with severe chronic GVHD live at least two years.

Steroid treatments work in about 50 percent to 65 percent of people with acute GVHD. When steroids don’t work, a person has a worse prognosis. Among people with GVHD that doesn’t respond to steroids, about 45 percent to 65 percent die within six months.

For about 1 out of 3 people with chronic GVHD, the disease is debilitating (makes someone become very weak or very sick). Some people with severe chronic GVHD have painful symptoms that last for years.

The closer a match your donor cells are to your own cells, the less severe your GVHD is likely to be. The higher the mismatch, the higher your chances of having a worse prognosis.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their loved ones. On MyLeukemiaTeam, members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with graft-versus-host disease? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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