Chronic graft-versus-host disease (GVHD) is a potential complication of a stem cell transplant that can significantly affect your quality of life. In GVHD, cells from donated bone marrow begin to attack your healthy tissue, leading to damage and symptoms that may be mild, severe, or even life-threatening.

Recognizing the symptoms of chronic GVHD can improve your likelihood of successful treatment. If you or a loved one has had a stem cell transplant or has been diagnosed with chronic GVHD, it’s important to learn all you can about this condition.

1. Chronic GVHD Can Develop at Any Time After a Transplant

Chronic GVHD typically develops 100 days or more after a stem cell transplant (also called a bone marrow transplant). However, it’s possible to develop chronic GVHD at any time.

Chronic GVHD is different from acute GVHD in several ways. It’s also possible to have both acute and chronic GVHD at the same time. If both types of GVHD occur at the same time, it’s known as overlap syndrome.

You’ll begin taking immunosuppressant drugs before your transplant to lower the risk of GVHD. These drugs help prevent GVHD by weakening the immune response of the donor cells. A few months post-transplant, your healthcare team may begin to lower your immunosuppressant dose. You may be more likely to develop chronic GVHD around the time your immunosuppressant dose is reduced.

2. Chronic GVHD Is Common, but More Often Mild

Researchers estimate that between 40 percent and 70 percent of people who receive a stem cell transplant will develop chronic GVHD. However, most people who develop chronic GVHD have mild to moderate disease. About 40 percent of people may develop more severe symptoms.

3. Many Risk Factors Relate to the Donor

Chronic GVHD may be more likely when the donor cells (the graft) aren’t a perfect match for the transplant recipient (host). Tissue typing tests can help determine whether a donor is a good match by comparing the proteins on the surface of the cells — called human leukocyte antigens (HLAs) — of the donor and the transplant recipient. A donor with a perfect HLA match will have the same pattern of HLA proteins as the transplant recipient. The more HLA matches between a donor and recipient, the lower the risk of developing GVHD.

Parents and full-blooded siblings have the highest chance of being a good HLA match. That’s because HLA proteins are inherited from your parents. You may also be able to find a good match in a donor registry. However, it’s often more difficult for people of color to find a perfect HLA match in a donor registry, according to the University of Texas MD Anderson Cancer Center. Compared to getting a transplant from a parent or sibling, the risk of GVHD is higher in people receiving a transplant from an unrelated donor.

Other risk factors for developing chronic GVHD, according to the Leukemia & Lymphoma Society, include:

• Receiving a transplant at an older age
• Receiving a transplant from an older donor
• Having a female donor for a male recipient
• Having a female donor who’s been pregnant in the past
• Receiving donated cells collected from peripheral blood instead of from bone marrow or umbilical cord blood
• Having a history of acute GVHD

4. Chronic GVHD Involves Inflammation and Scarring

In chronic GVHD, the donor immune cells begin to attack healthy tissue in the host instead of just attacking and killing diseased or cancerous blood cells. These attacks cause inflammation. If the inflammation continues over a long period of time, it damages tissues. Over time, damaged tissue is replaced with scar tissue in a process called fibrosis. The scar tissue doesn’t work as well as normal tissue, causing issues that can affect your health and quality of life.

5. Chronic GVHD May Affect Many Different Organs

Chronic GVHD can affect any organ in the body. It’s possible to have just one affected organ or area of the body, but it’s more common to have more than one organ affected by chronic GVHD.

Chronic GVHD symptoms depend on which organ is affected. Common symptoms may include:

• Skin — Rash, dryness, itching, skin thickening, and ulcers that don’t heal on their own
• Mouth — Dry mouth, pain or sensitivity while eating or drinking, difficulty eating or swallowing, and tooth decay
• Eyes — Dry eyes, blurry vision, light sensitivity, and possibly blindness
• Liver — Jaundice (yellowing of the skin and whites of the eyes) and stomach swelling
• Gastrointestinal (digestive) tract — Weight loss, decreased appetite, diarrhea, nausea, vomiting, and stomach pain

Other symptoms that may be related to chronic GVHD may include:

• Loss of hair or nails
• Shortness of breath
• Joint stiffness
• Muscle weakness
• Genital itching or pain

Your healthcare team will grade chronic GVHD based on how severe your symptoms are and how many organs are affected. Chronic GVHD is graded as mild, moderate, or severe.

6. Other Conditions Must Be Ruled Out To Diagnose GVHD

Chronic GVHD symptoms usually aren’t specific to chronic GVHD. That means they could be caused by many other medical conditions. If you begin to experience new symptoms after a stem cell transplant, your healthcare team will need to run tests to rule out other conditions and confirm GVHD.

You may be referred to a specialist based on the organ that’s affected. For example, if your skin is affected, you’ll see a dermatologist. If your mouth, gastrointestinal tract, or liver is affected, you’ll see a gastroenterologist.

The specialist will order tests to help diagnose chronic GVHD. The type of tests depend on which organs are affected. Sometimes, your healthcare team has to take a sample of the affected tissue — this is known as a biopsy. Looking at the tissue sample under a microscope can help your doctor understand the cause of your symptoms. Other tests for chronic GVHD may include blood tests, lung function tests, or imaging tests.

The National Institutes of Health have set guidelines to diagnose chronic GVHD. According to these criteria, a person must show a clear sign of the disease in organs like the skin, mouth, lungs, or genitals, or have a suspicious sign that is later confirmed by a biopsy or other test. Some signs, such as skin rashes, mouth ulcers, or dry eyes, are not enough by themselves because other issues might cause them, so additional testing is needed.

7. Most People Will Need Long-Term Treatment

Once it develops, chronic GVHD may last for years, or even the rest of your life.

The first-line treatment — the one usually prescribed first — for chronic GVHD is corticosteroids (steroids), such as prednisone. Steroid drugs help with chronic GVHD by suppressing the immune system and decreasing inflammation. If you have mild symptoms that only affect one part of your body, you may only need local or topical steroid treatment. That could include a steroid cream for a rash or a steroid eye drop for eye problems. If you have severe symptoms or have multiple organs affected, you’ll need systemic (whole-body) treatment taken by mouth or intravenously (by IV).

Sometimes steroids are combined with other immunosuppressants, such as:

• Cyclosporine (Gengraf, Neoral)
• Sirolimus (Rapamune)
• Tacrolimus (Prograf)

Some of these drugs are FDA-approved to treat rheumatoid arthritis, psoriasis, or to prevent organ rejection after a transplant. However, doctors may prescribe them off-label for GVHD when studies suggest the benefits outweigh the risks, even though they aren’t specifically FDA-approved for this use.

About half of people with chronic GVHD need immunosuppressant treatment for longer than two or three years. In some cases, life-long treatment may be needed.

If chronic GVHD doesn’t improve with steroid treatment, it’s considered steroid-refractory. If you have steroid-refractory chronic GVHD, you’ll need treatment with second-line therapies.

8. Outlook Depends on Severity and Early Treatment

Severe chronic GVHD is associated with an increased risk of death compared to mild disease. Having mild GVHD may actually be a positive sign. Studies show that mild GVHD is associated with a lower risk of relapse (return) of blood cancer such as leukemia or lymphoma.

However, chronic GVHD can also be life-threatening when it becomes severe. About 15 percent of the deaths that occur more than 100 days after transplant are related to chronic GVHD. It’s important to watch for new or unusual symptoms and report them to your healthcare team immediately. It’s a good idea to examine your body at least once a week to check for chronic GVHD symptoms. Finding chronic GVHD early and getting treatment early can improve your outlook.

Talk With Others Who Understand

On myGVHDteam, the site for people with GVHD and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with GVHD.

Have you or a loved one been diagnosed with chronic GVHD? What questions do you have about chronic GVHD? Share your experience in the comments below.