Graft-versus-host disease (GVHD) is a serious complication that can occur after a stem cell transplant. GVHD causes the immune system to attack the transplanted cells, leading to damage in various parts of the body, including the skin, gastrointestinal (digestive) tract, and liver. This disease can have a major impact on quality of life and is responsible for more than 10 percent of posttransplant deaths.

Doctors can take steps before and after a transplant to lower the risk of GVHD. Understanding these approaches can help you or your loved one more confidently navigate the transplant process.

Steps Toward Getting the Best Match

Before a stem cell transplant, one of the most important steps is finding a donor whose cells closely match the recipient’s. A good match can lower the risk of GVHD.

Certain donor-recipient factors are linked to a high risk of GVHD. These risk factors include:

• Human leukocyte antigen (HLA) mismatch — The HLA system is a group of proteins found on most cells. The closer the HLA match, the lower the risk of GVHD.
• Sex mismatch — A donor and recipient of different sexes may have a higher risk.
• Pregnancy history — Donors who have been pregnant may increase the risk of GVHD due to exposure to different immune markers.
• Older donor or recipient — Generally, older donors and recipients have a higher risk.
• Peripheral blood transplant — Transplants that use stem cells from the bloodstream (instead of bone marrow) are linked to a higher GVHD risk.

Doctors test both the recipient and potential donors to find the best HLA match. However, a perfect match isn’t always available. In these cases, doctors may recommend antithymocyte globulin (ATG), a therapy made from rabbit or horse antibodies. Studies show that ATG helps lower the risk of severe acute GVHD and chronic GVHD by targeting T cells and B cells — immune cells that play a role in the disease. Acute GVHD occurs within the first 100 days after transplant and mainly affects the skin, liver, and gut, whereas chronic GVHD is a longer-term condition that can affect multiple organs and tissues.

Current Regimens for the Prevention of GVHD

Doctors combine two types of medication to help prevent GVHD — antimetabolites and calcineurin inhibitors. Antimetabolites include drugs such as methotrexate or mycophenolate mofetil, which slow the growth of immune cells that contribute to GVHD. Calcineurin inhibitors such as tacrolimus and cyclosporine help suppress the immune system. This combination treatment has been the standard for nearly 40 years.

A newer approach uses posttransplant cyclophosphamide, a drug originally thought to destroy the T cells that cause GVHD. However, recent research suggests that instead of eliminating T cells, cyclophosphamide makes them less active, helping prevent GVHD while preserving immune function.

Studies show that using high-dose cyclophosphamide along with standard treatment leads to better outcomes than the two-drug approach alone. In one major study, researchers compared the standard treatment with an experimental three-drug combination of cyclophosphamide, mycophenolate mofetil, and tacrolimus. The results showed that fewer people developed GVHD with the experimental treatment, which also didn’t worsen survival rates, increase infections, or lead to more relapses. Because of this, researchers think this three-drug approach could become the new standard to prevent GVHD.

Some findings suggest that adding prednisone to standard treatment (methotrexate plus cyclosporine) may further lower the risk of GVHD. Your healthcare provider can help determine the best treatment plan based on factors such as side effects, medical history, and transplant details.

New Approaches for Preventing GVHD

GVHD affects about half of those who receive a donor transplant. Although several treatments can help manage GVHD, researchers are also exploring new ways to prevent it from developing in the first place.

One promising approach involves the drug abatacept (Orencia). Studies show that combining abatacept with methotrexate and a calcineurin inhibitor lowers the risk of acute GVHD. Because of these findings, the U.S. Food and Drug Administration (FDA) approved abatacept to help prevent acute GVHD in people receiving a stem cell transplant.

Researchers are also looking into how antibiotics may influence GVHD risk. Antibiotics are commonly given during the transplant process to prevent infections, but they can also disrupt the body’s natural microbiome — the community of helpful bacteria that support immune system function. Scientists believe that the type and timing of antibiotics could play a role in GVHD risk. Understanding this connection may lead to new ways to prevent GVHD by preserving a healthier microbiome.

The Importance of Posttransplant Monitoring

GVHD can develop at different times after a stem cell transplant. Acute GVHD typically occurs within the first 100 days, whereas chronic GVHD usually develops after that period but within the first two years. Because GVHD can appear at any stage, it’s important to stay alert for symptoms even after the initial recovery period.

Acute GVHD usually affects the skin, gastrointestinal tract, and liver. Symptoms to watch out for in the first 100 days of a transplant include:

• Diarrhea, nausea, or vomiting
• Rash (may look like a sunburn)
• Stomach cramps
• Jaundice (yellowing of the skin or eyes)

Chronic GVHD can affect the lungs, skin, muscles, and other body systems. Symptoms vary but may include:

• Dry mouth or eyes
• Hair loss
• Itchiness in the vagina or scrotum
• Muscle pain or weakness
• Persistent cough
• Limited range of motion
• Skin tightness
• Swelling

GVHD isn’t always preventable, but early treatment can help manage symptoms and prevent complications. Be sure to let your healthcare provider know if you notice any symptoms that could indicate GVHD. To diagnose GVHD, your doctor may:

• Perform a physical exam
• Take a biopsy (a small sample of skin or tissue for lab testing)
• Order imaging or blood tests

Recognizing GVHD early gives doctors a better chance to slow its progression and reduce long-term effects.

Communicate With Your Healthcare Provider

Researchers are still uncovering new ways to prevent GVHD by improving standard treatments and testing new approaches. Before making treatment decisions, it’s important to weigh the benefits, risks, and potential side effects with your healthcare team.

GVHD prevention and management involves collaboration among several providers. Your care team may involve multiple specialists, including:

• Primary care provider — Oversees general health and ongoing care
• Transplant specialist — Focuses on the transplant process and follow-up
• Oncologist or hematologist — Manages cancer or blood disorders
• Pharmacist — Helps with medication safety and side effects
• Nutritionist — Provides guidance on diet and gut health
• Nurses and other providers — Offer education and support

Don’t be afraid to ask questions regarding your treatment options or explore different approaches. Understanding what to expect can help you or your loved one feel more confident in managing health after a transplant and recognizing the signs of GVHD.

Talk With Others Who Understand

On myGVHDteam, the site for people with graft-versus-host disease and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with the condition.

Do you have firsthand experience with any of the approaches to help prevent GVHD? Share your thoughts in the comments below.