Graft-versus-host disease (GVHD) is a complication that can develop in people who have undergone a bone marrow or stem cell transplant from a donor. It occurs when immune cells in the donated tissue (graft) recognize the recipient (host) as foreign and mistakenly attack other tissue in the transplant recipient’s body.

Allogeneic (donor) bone marrow and stem cell transplants are used to treat blood cancers such as leukemia and lymphoma. A bone marrow transplant is a type of stem cell transplant in which the cells come from bone marrow. In a stem cell transplant, the cells can come from another person’s blood or blood from a baby’s umbilical cord, according to the American Cancer Society.

In either case, a transplant is intended to replace your bone marrow with healthy stem cells to treat the cancer. “We would do a lot more transplants, but this immune system attack on the healthy tissue (GVHD) is a major obstacle that can offset some of that benefit,” says John Levine, MD, a hematologist-oncologist at Mount Sinai Hospital in New York City.

GVHD symptoms can be mild, moderate, severe, or life-threatening.

Types of GVHD

These are two common types of GVHD that occur in bone marrow and stem cell recipients.

Acute GVHD

Acute GVHD usually develops in the weeks or months after a transplant, but it can also develop later.

The most common symptoms, which tend to appear and worsen over a matter of days, are a red skin rash, diarrhea, vomiting, and abnormal liver function tests. Symptoms that occur three months or more after the transplant are called late acute GVHD. Up to 50 percent of patients receiving a stem cell transplant from a sibling develop GVHD. (See Risk Factors for GVHD for an explanation of human leukocyte antigens.) That rate is typically higher with unmatched donors.

Chronic GVHD

Chronic GVHD typically develops within one year of a transplant. It can affect up to 80 percent of stem cell transplant recipients.

Almost any organ or tissue can be affected by chronic GVHD, but common symptoms include skin rash and thickening; muscle and joint stiffness; dry eyes and dry mouth; weight loss; and difficulty breathing. Chronic GVHD can also cause many other symptoms that often develop slowly, over weeks to months.

According to Cleveland Clinic, after an allogeneic stem cell transplant, it’s possible to develop one or both forms of GVHD — or neither.

Risk Factors for GVHD

When preparing a person with blood cancer for an allogeneic stem cell transplant, doctors look at their human leukocyte antigens (HLA), which are proteins, or markers, found on cells. The immune system uses these to recognize which cells belong to the recipient and which are foreign to their body.

Because these markers are inherited, recipients have a 25 percent chance of being a full, or complete, match with a sibling. But 70 percent of people who need a stem cell transplant don’t have a fully-matched donor in their family.

The greatest risk factor for acute GVHD is a poor match between the recipient’s and the donor’s HLA. The more mismatched, the greater the risk. Recipients are more likely to be well-matched with someone of a similar ancestry or ethnic background.

Other risk factors include being an older patient, grafting with growth factor-mobilized blood cells (peripheral blood), and having a female donor if the recipient is male.

“Blood cancer patients also tend to undergo chemotherapy, with or without radiation, before a bone marrow or stem cell transplant, and a higher intensity of therapy can increase the risk for GVHD,” says Doris Ponce, MD, an associate professor of medicine and the program director of GVHD at Memorial Sloan Kettering Cancer Center in New York City.

With chronic GVHD, the greatest risk factor is having already experienced acute GVHD. Other risk factors, as with acute GVHD, are a greater HLA mismatch and an older transplant recipient.

GVHD Symptoms

Acute and chronic GVHD have some symptoms that overlap, as well as others that are unique to each type.

Symptoms of Acute GVHD

Acute GVHD can affect the skin, gastrointestinal (GI) tract, and liver. Symptoms can include:

Skin rash with burning and redness anywhere on the body, including the palms of the hands and soles of the feet; skin may blister or flake off in severe cases
Nausea, vomiting, abdominal cramping, and diarrhea
Yellowing of the skin or eyes (jaundice), along with abnormal blood test results (signs of liver problems)

Symptoms of Chronic GVHD

Chronic GVHD can involve one organ or several.

Symptoms may include:

Skin Problems

Dry, itchy skin
Skin rash
Skin thickening and tightening
Intolerance to temperature changes (due to damaged sweat glands)
Change in skin color

Liver Problems

Abdominal swelling
Yellowing (jaundice) of the skin or eyes
Abnormal blood test results

Nail and Hair Problems

Changes in nail texture
Nail loss
Hair loss on scalp or body
Premature gray hair

Eye Problems

Dry eyes
Vision changes

Oral Problems

Dry mouth
Pain or sensitivity to spicy foods
White patches inside the mouth

Lung Problems

Shortness of breath
Chronic cough
Wheezing
Changes seen on a chest X-ray

GI Problems

Weight loss
Difficulty or pain when swallowing
Loss of appetite
Stomach pain
Nausea
Vomiting
Diarrhea

Nerve, Muscle, and Joint Problems

Muscle weakness
Muscle pain
Fatigue
Joint stiffness that makes it difficult to extend the fingers, wrists, elbows, knees, or ankles

Female Genital Problems

Vaginal ulcers and scarring
Narrowing of the vagina
Vaginal dryness, itching, and pain
Painful intercourse

Male Genital Problems

Penis irritation
Itching and scarring on the penis or scrotum

“It can sometimes be difficult to distinguish between acute and chronic GVHD. It’s always a good idea to review symptoms with the bone marrow transplant team, because sometimes the signs and symptoms can be subtle,” says Shernan Holtan, MD, the chief of the bone marrow and transplantation service at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

GVHD Diagnosis

Because GVHD is so common, patients are continuously monitored for symptoms after a bone marrow or stem cell transplant.

“GVHD is usually a diagnosis of exclusion, meaning that other potential explanations for the signs and symptoms need to be evaluated, including infections or medication side effects,” says Dr. Holtan.

Your oncologist will perform a physical exam and check your lab results for changes. If there are any changes, your doctor will first try to determine if the symptoms you’ve developed are due to other causes.

“Sometimes, biopsies of affected tissue are done to see if there are any changes,” says Dr. Levine.

In mild cases of chronic GVHD, the symptoms can seem vague or due to something else. It’s important to tell your care team about any new symptoms you experience, to rule out the possibility of GVHD.

GVHD Treatment Options

Treatment options are straightforward and will depend on the type of GVHD you have, which parts of your body are affected, and the disease’s severity.

Acute GVHD Treatment

If your symptoms are mild, treatment can be simple. “If only the skin is affected and this affection is limited, patients can use a steroid topical treatment like a cream or ointment,” says Dr. Ponce.

If acute GVHD symptoms are more severe or affect more of your body, it’s first treated with corticosteroids to suppress the immune system. These can include medications such as:

prednisone
methylprednisolone
dexamethasone
beclomethasone
budesonide

If steroids don’t work, your doctor may prescribe another type of immune system-suppressing medication known as ruxolitinib. Otherwise, your doctor may choose to prescribe a different medication for off-label use, Levine says. Off-label drug use happens when physicians prescribe a medication for an indication not yet approved by the U.S. Food and Drug Administration.

Chronic GVHD Treatment

As with acute GVHD, mild cases of chronic GVHD that affect a single organ can be treated with local therapies, such as a steroid skin cream or steroid eye drops.

If you have more severe symptoms, or more organs are affected, you may be treated with systemic corticosteroid medications, such as prednisone.

If you don’t respond to steroid treatment, your doctor can prescribe another type of immunosuppressant, such as:

ruxolitinib
belumosudil
ibrutinib

It’s also possible to seek treatment through clinical trials, adds Holtan. Researchers continue to look into other GVHD treatment options that can replace steroids, since steroids suppress your immune system and can make you more susceptible to infections or illnesses when taken for long periods of time.

GVHD Prevention

Before a stem cell or bone marrow transplant, doctors will take several steps to help reduce the likelihood and severity of GVHD.

T cells, a type of white blood cell that develops from stem cells in bone marrow, are part of the immune system and can help fight cancer. Doctors may remove T cells from the donor graft or give medications to suppress the T cells, so they are less likely to attack your cells.

Then, starting three days after the transplant and continuing for several months, doctors often prescribe a regimen of three immunosuppressant drugs:

cyclophosphamide, a chemotherapy drug
tacrolimus
mycophenolate mofetil

By waiting three days after a transplant to prescribe the drug regimen, the donor cells have time to react to the patient. Once those cells divide, they are more susceptible to the chemotherapy, says Levine.

“This approach tends to eliminate a lot of the cells that are gearing up to go on a ‘killing spree,’ while preserving the regulatory side of the immune system,” Levine adds.

Together, all three drugs work to help lower your GVHD risk.

Outlook for GVHD

Although most people who develop GVHD can be treated, more than 10 percent die from it.

“People with acute GVHD have a higher risk of complications and a higher risk of mortality,” says Ponce.

Among those who survive GVHD, symptoms can be treated with medications, but they may not go away completely. “Most of the treatments can result in some decrease in the symptom burden, but the treatments currently available don’t result in a complete response for most patients,” explains Levine.

Even if medications don’t eliminate your symptoms altogether, they are intended to help improve organ function, increase quality of life, and alleviate symptoms with the fewest side effects possible, says Holtan.

“Overall, this is a very nuanced issue that requires careful discussion with your transplant physician, as the prognosis may vary widely from patient to patient,” Holtan adds.

Conor Steuer, MD

Medical Reviewer

Conor E. Steuer, MD, is medical oncologist specializing in the care of aerodigestive cancers, mesothelioma, and thymic malignancies and an assistant professor in the department of hematology and medical oncology at the Emory University School of Medicine in Atlanta. He joined the clinical staff at Emory's Winship Cancer Institute as a practicing physician in July 2015. He currently serves as chair of the Lung and Aerodigestive Malignancies Working Group and is a member of the Discovery and Developmental Therapeutics Research Program at Winship.

Dr. Steuer received his medical degree from the New York University School of Medicine in 2009. He completed his postdoctoral training as a fellow in the department of hematology and medical oncology at the Emory University School of Medicine, where he was chief fellow in his final year.

He has been active in research including in clinical trial development, database analyses, and investigation of molecular biomarkers. He is interested in investigating the molecular biology and genomics of thoracic and head and neck tumors in order to be able to further the care of these patient populations. Additionally, he has taken an interest in utilizing national databases to perform clinical outcomes research, as well as further investigate rare forms of thoracic cancers.

Steuer's work has been published in many leading journals, such as Cancer, the Journal of Thoracic Oncology, and Lung Cancer, and has been presented at multiple international conferences.

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Erica Patino

Author

Erica Patino is a freelance writer and editor, content strategist, and usability specialist who has worked for a variety of online health outlets, including Healthline, Sharecare, and Twill Care. She was previously a senior editor at Everyday Health. She is also the founder and editor-in-chief of Hear 2 Tell, a website that covers advances in hearing loss treatment. Patino lives in Portland, Oregon, with her husband and twin sons.