There are four main types of graft-versus-host disease (GVHD), each defined by how quickly symptoms appear and how severe they become. The two most common types are acute GVHD and chronic GVHD. Acute GVHD comes on suddenly, while chronic GVHD develops slowly and can last a long time. Some people with acute GVHD later develop the chronic form, a condition known as overlap syndrome. There’s also late acute GVHD, which develops after the typical window for acute symptoms has passed.

This article will discuss these types of GVHD and what causes them. We’ll also cover their symptoms and what to watch for. If you notice any new or worsening signs of GVHD, talk to your oncology or transplant team. They can run tests to confirm the diagnosis and start a treatment plan.

1. Acute Graft-Versus-Host Disease

Acute GVHD develops in people who have recently had an allogeneic stem cell transplant. Also known as an allogeneic bone marrow transplant, this procedure uses healthy stem cells (cells that help make blood) from a donor. These donated cells replace damaged or diseased blood-forming cells, helping your body make healthy blood cells again. Allogeneic stem cell transplants are a treatment option for certain types of blood cancers like lymphoma and leukemia.

GVHD develops when donated T cells recognize the recipient’s healthy cells as foreign and attack them. Studies show that in acute GVHD, these T cells become activated, triggering inflammation that further damages healthy tissues.

What Causes Acute Graft-Versus-Host Disease?

Certain factors raise the risk of acute GVHD. Before a transplant, doctors run tests to check what kind of human leukocyte antigen (HLA) markers you have. HLA proteins are on most of your cells. They tell your immune system that your cells belong to you. Cells that have different HLA proteins get targeted and destroyed by your lymphocytes (white blood cells).

Everyone has different HLA markers, so it’s important to find out which you have. Stem cell transplants need to come from people with the same or similar HLA markers you have. Identical twins have the same markers, while unrelated people can have very close-matching proteins. HLA-mismatched donors raise the risk of GVHD.

The Leukemia & Lymphoma Society has found that you’re more likely to develop acute GVHD if:

• Your donor is unrelated, even if they have the same HLA markers as you.
• Your donor isn’t an exact HLA match.
• You or your donor is older.
• You’re male and receive cells from a female donor.

Read more details about what causes GVHD.

When and Where Does Acute Graft-Versus-Host Disease Develop?

Traditionally, doctors diagnosed acute GVHD when symptoms developed within 100 days (roughly three months) after a transplant. The National Institutes of Health (NIH) also updated the guidelines to consider how severe the symptoms are. Although most cases of acute GVHD occur within 100 days, some can develop later.

According to the Leukemia & Lymphoma Society, 30 percent to 70 percent of people who have allogeneic stem cell transplants eventually develop acute GVHD. Symptoms most often affect the skin, liver, and gastrointestinal (GI) tract. You may have mild, moderate, or severe symptoms. Some people even have life-threatening complications.

Skin problems are common and can develop anywhere on your body. Some people notice red rashes, while others may see dark patches or areas of discoloration, especially on the palms of their hands or the soles of their feet. GVHD can also affect your digestive system. Inflammation in your GI tract can cause diarrhea, vomiting, and nausea. In some cases, you may notice red blood in your stool as well.

Acute GVHD of the liver may not cause noticeable symptoms at first, but doctors can find it through blood tests that show high liver enzyme levels. In more serious cases, it can cause jaundice (yellowing of the skin or eyes). If left untreated, acute GVHD can lead to liver failure.

Grading Acute Graft-Versus-Host Disease

Acute GVHD may be mild, moderate, or severe. Once your doctor confirms that you have acute GVHD, they’ll assign different stages. Staging indicates how severe the disease is based on two factors: which organs are affected and how severe your symptoms are (the grade). Acute GVHD stages are numbered 1 through 4. Stage 1 is the most mild, while stage 4 is the most severe.

After your doctor stages your organs, they’ll then grade your overall acute GVHD. The grading is as follows:

• Grade 1 — Mild acute GVHD that affects up to one-quarter (25 percent) of your skin
• Grade 2 — Moderate acute GVHD that affects up to half (50 percent) of your skin and potentially your liver and GI tract
• Grade 3 — Severe acute GVHD that affects over half of your skin and the liver, plus severe GI symptoms like cramping and diarrhea
• Grade 4 — Very severe acute GVHD affecting your skin, GI tract, and liver

2. Chronic Graft-Versus-Host Disease

Chronic GVHD typically develops more than 100 days after your bone marrow transplant. The term “chronic” means long-term — many people diagnosed with this condition have symptoms for many years. Some can even have lifelong problems. Chronic GVHD varies in severity, affecting some people mildly while causing serious complications in others.

Doctors and researchers don’t understand chronic GVHD as well as acute GVHD. Many believe chronic GVHD is more complex and involves more aspects of the immune system. The long-term inflammation from this condition can affect more organs than acute GVHD. It also raises the risk of fibrosis — abnormal thickening of tissues throughout your body.

What Causes Chronic Graft-Versus-Host Disease?

Studies show there are some risk factors for developing chronic GVHD. If you’ve had acute GVHD before, you’re also more likely to develop chronic GVHD.

How the donated cells are collected can also affect your risk. For example, cells collected from the bone marrow — the spongy tissue inside the bones — are less likely to cause chronic GVHD than those collected from peripheral blood (the bloodstream).

Like acute GVHD, chronic GVHD also affects people who receive transplants that aren’t a perfect HLA match. The Leukemia & Lymphoma Society has found that males who receive donor cells from females are also at an increased risk. This is especially true if the female has been pregnant before.

Similarly, age is a risk factor in GVHD. Older people and donor age are associated with a higher risk of GVHD.

When and Where Does Chronic Graft-Versus-Host Disease Develop?

The Leukemia & Lymphoma Society notes that up to half of people who receive an allogeneic stem cell transplant develop chronic GVHD. This condition affects many more organs than acute GVHD.

Symptoms of chronic GVHD include:

• Mouth problems like open sores (ulcers), dry mouth, and trouble eating and swallowing
• Skin symptoms like rashes, dry skin, thickening around joints, and color changes
• Dry, itchy eyes and blurry vision
• Trouble breathing, coughing, and wheezing
• Nausea, vomiting, and diarrhea
• Hair loss
• Liver issues
• Muscle and joint issues like muscle cramps and weakness
• Problems in the genitals and sexual organs

3. Overlap Syndrome With Graft-Versus-Host Disease

If you have overlap syndrome, it means you were diagnosed with chronic GVHD while also having acute GVHD symptoms. Studies show that chronic GVHD symptoms in those with overlap syndrome have a major impact on quality of life. This is likely because chronic symptoms affect more organs — including the joints and lungs. When it comes to treatment, doctors treat overlap syndrome based on your chronic GVHD symptoms.

4. Late Acute Graft-Versus-Host Disease

Late acute GVHD is a type of acute GVHD that develops more than 100 days after a transplant. It can happen in three ways. In persistent GVHD, symptoms continue past day 100. In recurrent GVHD, the condition comes back after getting better for a while. Late-onset acute GVHD happens when medications that weaken the immune system are stopped. These medications help prevent the immune system from attacking the donor cells.

Doctors treat GVHD with medications that weaken the immune system, called immunosuppressants. These drugs help prevent the immune system from attacking the donor cells. Examples include corticosteroids (steroids) like prednisone. Stopping treatment can cause acute GVHD symptoms to return. Always follow your treatment plan and consult your doctor before making any changes.

When To Call Your Doctor

If you’ve had a stem cell transplant, watch for signs of GVHD like rashes, digestive issues, breathing problems, or fatigue. Staying in close contact with your transplant team helps you catch and manage symptoms early. If you notice any changes, call your doctor right away so they can adjust your treatment as needed. To learn more about treatment options, read more about how GVHD is treated.

Talk With Others Who Understand

On myGVHDteam, the site for people with graft-versus-host disease and their loved ones, people come together to gain a new understanding of GVHD and share their stories with others who live with the condition.

What symptoms or challenges have you experienced with GVHD, and how have you managed them? Share your experiences in the comments below.