In some people, an allogeneic stem cell transplant (alloSCT) can potentially cure lymphoma by replacing the immune system with cells from a healthy donor. However, after an alloSCT, the new immune system can sometimes cause harm as well as help.

Graft-versus-host disease (GVHD) happens when the transplanted cells attack the body’s own healthy tissues. The donated stem cells are called the “graft,” and your body is the “host.” GVHD causes a variety of symptoms, which vary from person to person.

This article covers basic facts about GVHD, including how healthcare teams treat and try to prevent it.

Why Does Graft-Versus-Host Disease Happen?

After an alloSCT, the donated cells grow into a new, functioning immune system. The immune system is made up of specialized white blood cells. One type, called a T cell, plays an important role in immunity and GVHD.

In GVHD, the new T cells mistake healthy cells for harmful invaders. They target organs and tissues, causing symptoms throughout the body.

One of the best ways to lower the risk of GVHD is to find the closest possible donor match. Nearly every cell in the body has markers that help the immune system recognize which cells belong there. These markers are called human leukocyte antigens (HLAs).

A donor’s HLA markers need to closely match your own. If the HLA markers don’t match well, the risk of GVHD is higher.

Who’s at Risk of Graft-Versus-Host Disease?

GVHD is a common side effect of alloSCTs. Nearly half of people who have an alloSCT eventually develop GVHD.

Risk factors for GVHD include:

• Getting HLA-matched stem cells from an unrelated donor
• Getting stem cells from a related donor with an HLA mismatch
• Getting stem cells from a donor who’s been pregnant before
• Being older (either the recipient or the donor)
• Having a donor of a different sex

How Is Graft-Versus-Host Disease Classified?

GVHD is classified as either acute or chronic. Acute GVHD starts soon after a donor stem cell transplant, usually within several days to weeks. Chronic GVHD can begin a few months to two years after the transplant.

Acute Graft-Versus-Host Disease

Acute GVHD begins within the first 100 days after an alloSCT. The immune system may attack the skin, liver, or gastrointestinal (GI) tract, which includes the stomach and intestines.

Symptoms of acute GVHD may include:

• Skin rashes
• Nausea, vomiting, and diarrhea
• Jaundice (yellowing of the skin and whites of the eyes)

In severe cases, acute GVHD can cause:

• Skin blistering and peeling
• Blood in the stool
• Liver failure, leading to confusion, fluid buildup, and bleeding

Doctors use a staging and grading system to find out how severe acute GVHD is. Each affected organ is given a stage from 1 through 4. Stage 1 is the mildest, and stage 4 is the most severe.

Once each organ is staged, doctors combine the results into an overall grade. Grades 3 and 4 acute GVHD are more severe and are linked to a higher risk of complications and a worse prognosis (outlook).

Chronic Graft-Versus-Host Disease

Chronic GVHD develops more slowly. Symptoms can appear anytime but usually show up within 100 to 600 days after an alloSCT.

Chronic GVHD affects many parts of the body. Signs and symptoms depend on which organs are involved. Examples include:

• Eyes — Dry or itchy eyes, blurry vision, and (in some cases) vision loss
• Mouth — Dry mouth, painful sores, and difficulty eating or swallowing
• Skin — Rashes, open sores, and changes in skin color
• Hair — Hair loss on the head or body
• Liver — Jaundice and belly swelling
• Lungs — Wheezing and shortness of breath
• GI tract — Nausea, vomiting, diarrhea, stomach pain, and loss of appetite

As the name suggests, symptoms of chronic GVHD can last many years. Some people may live with the condition for the rest of their lives.

How Is Graft-Versus-Host Disease Treated?

GVHD treatment focuses on managing symptoms and preventing more organ damage. Everyone who has an alloSCT takes immunosuppressive drugs to help prevent GVHD. These medications lower immune system activity so it’s less likely to attack the body.

Some people still develop GVHD even with immunosuppressants. Treatment depends on the symptoms. For example, mild skin rashes may be treated with topical corticosteroid (steroid) creams.

If GVHD symptoms are widespread, you’ll continue taking immunosuppressant drugs. These medications work throughout the body to control inflammation. Your doctor may also prescribe an oral steroid to further reduce the immune response.

Steroid-Refractory Graft-Versus-Host Disease

Some people with acute and chronic GVHD don’t respond to steroid treatment. This is known as steroid-refractory GVHD.

The U.S. Food and Drug Administration (FDA) has approved several medications for steroid-refractory GVHD. These include ibrutinib (Imbruvica), which is also approved to treat some types of NHL, along with:

• Axatilimab-csfr (Niktimvo)
• Belumosudil (Rezurock)
• Remestemcel-L-rknd (Ryoncil)
• Ruxolitinib (Jakafi)

Extracorporeal photopheresis (ECP) is another treatment option for steroid-refractory GVHD. ECP uses a light-sensitive chemical and ultraviolet (UV) light to change how the immune system works.

During ECP, you’re hooked up to a machine that separates T cells from the blood. The cells are treated with a plant-based chemical called 8-MOP and exposed to UV light. The cells are then returned to the bloodstream.

Researchers aren’t sure just how ECP treats GVHD. They believe the treated T cells become less active, making them less likely to attack healthy organs. This may help reduce inflammation and swelling.

Supportive Treatments for Graft-Versus-Host Disease

Depending on your GVHD symptoms and treatment plan, you may also need supportive care. For example, people with GVHD symptoms affecting the GI tract may need IV nutrition to stay healthy. Medications such as octreotide, which may be prescribed off-label (for a use other than its approved one), can help treat diarrhea related to GVHD.

Immunosuppressants and steroids can cause side effects, including a higher risk of infections. Your doctor may prescribe medications to lower your risk of getting sick.

How Can You Prevent Graft-Versus-Host Disease?

Doctors take several steps before an alloSCT to lower the risk of GVHD. One of the most important is to find a donor who’s a good HLA match. A sibling with matching HLA markers is usually an ideal donor.

Some people receive stem cells from a half-matched donor. Parents, children, and siblings may be candidates. However, half-matched transplants carry a higher risk of GVHD.

Doctors give medication to dampen the immune system as well. These drugs help keep T cells from attacking healthy cells. Examples include:

• Biologics that reduce inflammation
• Chemotherapy drugs that destroy donor T cells
• Corticosteroids that calm the immune system and reduce inflammation
• Immunosuppressants that lower the immune response

What Are the Benefits and Risks of Graft-Versus-Host Disease?

One benefit of having GVHD is that your immune system also attacks your lymphoma cells. This can help get rid of any cancer left behind after treatment. Overall, GVHD lowers the risk of lymphoma coming back.

On the other hand, GVHD can become serious and even life-threatening. According to Cleveland Clinic, chronic GVHD is the leading cause of death after an alloSCT.

Your doctor will help you weigh the risks and benefits of an alloSCT based on your specific situation.

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