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Chronic Graft-Versus-Host Disease (GVHD)

Like the acute form, chronic GVHD also begins with donor immune cells (the graft) that, once transplanted inside your body (the host), view your organs and tissues as foreign and begin an attack. But chronic GVHD looks and acts differently than acute GVHD.

It tends to develop and progress more subtly and slowly. Most patients develop symptoms sometime within the first year after transplant, and a small percentage develop it later. It can affect many organs and tissues. And while there’s still much to be learned about all the biology at work, researchers now recognize that the chronic GHVD processes in the body are more varied and complex than with acute GVHD.

While both types involve an inflammatory reaction, for instance, chronic GVHD can also involve some degree of tissue drying (known as sicca) and tissue scarring and thickening (known as fibrosis). These are the same hallmarks of autoimmune diseases – like psoriasis, scleroderma, and rheumatoid arthritis. Autoimmune diseases also occur when the body’s immune system attacks healthy organs by mistake. Other symptoms of chronic GVHD - like eye dryness, muscle pain, and breathing trouble - can mimic dozens of other conditions and reactions.

To diagnose chronic GVHD, doctors often use exams and tests to make sure your symptoms aren’t caused by something else.

Signs and Symptoms of Graft-versus-Host Disease

Graphic of a man with dots in places where organs would be
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  • Very faint to severe sunburn-like rash
  • Blisters
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  • Jaundice (your skin or eyes look yellow)
  • Dark tea-colored urine
  • Pain in the upper part of your belly
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  • Nausea that doesn’t go away
  • Loss of appetite
  • Vomiting
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  • Diarrhea
  • Belly pain that doesn’t go away
  • Feeling bloated or full of gas
  • Blood in your stool
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  • Dry eyes
  • Irritation that won’t go away
  • Blurred vision
  • Teary eyes
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Mouth and Throat

  • Painless, lacy white lines on tongue or inner cheeks
  • Sores or irritation
  • Trouble opening your mouth
  • Pain and sensitivity to temperature and spices
  • Dry mouth, increasing risk for cavities along gums and between teeth
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Nervous System

  • Weakness, tingling, numbness in legs and feet
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  • Cough that doesn’t go away
  • Shortness of breath
  • Trouble breathing
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Digestive System

  • Nausea or vomiting
  • Diarrhea
  • Belly pain or cramping
  • Liver symptoms, such as yellowing of the eyes or skin
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  • Irritation or dryness
  • Rash
  • Painful intercourse
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Skin, Nails, and Hair

  • Skin texture changes (thickening)
  • Nail changes
  • Rash
  • Unusual hair loss or thinning
  • Itchy skin
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Joints and Muscles

  • Arthritis-like symptoms (pain and stiffness)
  • Muscle aches or pain, cramps, or weakness
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Contact your transplant team right away if you notice any of these signs or symptoms or if new ones develop after you start treatment. Early diagnosis and intervention are important!

What’s happening in my body?

Because there’s still so much to learn about the complexities of chronic GVHD, scientists are still not certain exactly how or why it affects some transplant patients more severely than others.

Acute GVHD mainly involves immune cells called T cells. Chronic GVHD, however, involves a complex interplay that involves both T cells and B cells. In healthy bodies, B cells typically produce antibodies that help fight threats from outside the body, such as bacteria and viruses. But in chronic GVHD, B cells can produce autoantibodies. These “confused” antibodies are directed against the host’s own cells inside the body. These are similar to autoantibodies seen in autoimmune diseases, in which the immune system becomes “corrupted” and attacks normal, healthy cells in the body.

Based on the research to date, transplant experts broadly explain chronic GVHD as a three-phase process in the body.

Phase 1: Early inflammation and tissue injury

Some early inflammation in the body happens because of the radiation and chemotherapy patients receive as part of their pre-transplant preparation (known as conditioning). Doctors sometimes refer to this as the “red” phase because of the skin rashes and other signs of inflammation that often start during this phase.

Phase 2: Ongoing inflammation and breakdown in the normal immune system checks and balances

This is the longest phase of chronic GVHD. More tissue injury occurs. And certain immune cells (known as regulatory T cells) that normally help to maintain order in the immune system start to decrease in number or don’t work as well. The immune system starts making mistakes and learning to behave in an abnormal way.

Phase 3: Abnormal tissue repair and fibrosis (scarring)

If phase 2 goes on long enough, the body’s ability to properly repair its damaged tissues also suffers. As a result, the body deposits too much collagen and other tissue-repair components around the tissues and organs that GVHD has inflamed or damaged. That creates thickening and scarring on the affected organs. If too much of this fibrosis occurs, it may lead to irreversible organ damage.

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Did You Know?

With chronic GVHD, most people remain on some type of therapy for 2 to 3 years, but this can vary. Some patients’ GVHD must be managed for longer periods.

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How Common Is Chronic GVHD?

  • 30% to 70% of patients who receive donor stem cells develop chronic GVHD
  • About 90% of patients who develop chronic GVHD do so within 1 year after transplant. After that, the risk tends to get lower.
  • 2 out of 3 patients who develop chronic GVHD had prior acute GVHD
Image of a man sitting and typing on his phone Image of a man sitting and typing on his phone
Image of Josh O.

I had GVHD, a head to toe rash, not long after leaving the hospital. And I still have some skin and mouth GVHD two years later….I try to stay positive, focus on today and tomorrow, bringing joy to people’s lives and finding joy in mine.

Josh O.

2018 transplant recipient