Graft vs. host disease (GVHD)

This page was reviewed under our medical and editorial policy by

Jeremy Larsen, MD, Hematologic Oncologist

This page was updated on May 22, 2023.

Graft vs. host disease (also graft-versus-host disease or GVHD) typically occurs after a cancer patient has received a donation of stem cells or bone marrow from another person, called an allogeneic transplant. Immune system cells in the donation (graft) attack the recipient’s (host’s) tissues. This reaction may range from mild to life-threatening.

What is GVHD?

GVHD is a complication that develops as a result of a tissue transplant from another person. In preparation to receive a stem cell transplant, a patient has his or her own immune system largely destroyed by chemotherapy drugs or radiation therapy. After the transplant, the new, donated cells essentially become the patient’s new immune system.

Immune cells check for the presence of certain proteins, called human leukocyte antigens (HLA), on cells they encounter to determine whether they’re cells belonging to the body or foreign cells targeted for attack. Because immune cells in the transplant come from another person, the cells may see the host’s tissues as foreign and attack them. That scenario causes GVHD.

To limit the likelihood and strength of these reactions, doctors look for donors who closely match the recipient’s HLA and gender. The National Library of Medicine estimates GVHD occurs in about 35 percent to 45 percent of transplants when the donor is a relative, and about 60 percent to 80 percent when a relative isn’t the donor. Doctors provide treatment to prevent or limit GVHD, which may include medicines to suppress T-cells (a type of white blood cell or leukocyte) in the donation or removal of T-cells from the donation. Some drugs given to prevent GVHD include:

  • Corticosteroids, such as prednisone and methylprednisolone
  • Immunosuppressives, including cyclosporine, tacrolimus and methotrexate
  • Monoclonal antibodies, such as alemtuzumab

While removing T-cells may reduce the risk of GVHD, it may raise the chances of some serious complications, including:

  • Viral infection
  • Graft failure
  • Leukemia relapse

Scientists are working on ways to remove just a subtype called alloactivated T-cells, which would permit the remaining donated T-cells to attack cancer cells.

Types of GVHD

Doctors divide GVHD into two types—acute and chronic—based on how long after a transplant symptoms appear:

Acute GVHD begins between a few days to three months after the transplant and doesn’t last a long time.

Chronic GVHD begins three to 20 months after the transplant and may persist throughout the patient’s life.

It’s possible to experience acute or chronic GVHD, both or neither. The American Cancer Society estimates that about 33 percent to 50 percent of allogeneic transplant patients develop acute GVHD.

GVHD symptoms

Both forms of GVHD may start with a rash or redness on the palms of the hands and soles of the feet. Both acute and chronic forms may raise the risk of bacterial infections and affect the skin and liver.

Additionally, acute GVHD often affects:

  • Kidneys
  • Intestinal tract

Chronic GVHD may affect:

  • Eyes
  • Mouth
  • Lungs
  • Muscles and joints

Some cases of chronic GVHD may not have symptoms or need treatment.

Acute GVHD symptoms

  • Rash or inflammation of skin on the palms and bottoms of the feet, with a burning sensation that may spread to the trunk and extremities
  • Skin blisters and peeling (severe cases)
  • Loss of appetite
  • Nausea or vomiting
  • Stomach cramps or abdominal pain
  • Diarrhea (may persist despite fasting and may progress to becoming bloody)
  • Weight loss
  • Jaundice (skin and whites of the eyes appear yellowish)
  • Abnormal liver function results in blood tests

Chronic GVHD symptoms

  • Rash or inflammation of skin on the palms and bottoms of the feet that feels dry and itchy and that may spread
  • Skin blisters and peeling (severe cases)
  • Other changes in skin, including scleroderma (skin loses elasticity and becomes stiff)
  • Injury to sweat glands
  • Vaginal dryness, itching, pain or ulcers
  • Painful intercourse
  • Penile irritation, itching or scarring
  • Scarring or narrowing of urethra
  • Vision changes, or dry or burning eyes
  • Premature gray hair or thinning hair
  • Nail changes or loss
  • Dry mouth, gum disease, tooth decay or mouth sores
  • Sensitivity to hot, cold, spicy or acidic foods (may experience burning sensation)
  • Decreased appetite
  • Diarrhea
  • Weight loss
  • Jaundice
  • Enlarged abdomen
  • Abdominal pain
  • Lung damage, causing shortness of breath, cough and wheezing
  • Pericarditis (inflammation of the membrane enclosing the heart)
  • Cytopenia (drop in levels of mature blood cells)
  • Stiff or painful joints
  • Fatigue and chronic pain
  • Muscle weakness

GVHD treatment

The care team will choose the appropriate treatment for GVHD based on whether the condition is acute or chronic.

Acute GVHD treatment

Treatment for acute GVHD varies with severity. People with mild cases affecting only the skin may use a steroid skin cream in addition to the immunosuppressant drugs they were given after the transplant. Patients with more severe systemic, whole-system or bodywide acute GVHD may be given another corticosteroid in addition to the immunosuppressants prescribed as preventatives post-transplant.

Chronic GVHD treatment

Mild cases of chronic GVHD, in which symptoms affect one area or organ (such as the skin or eyes), may have a treatment focus on that site. Systemic or whole-body treatment may be used for people with more severe cases affecting multiple organs.

Prednisone or related steroids form the standard first line of treatment for chronic GVHD. Combinations of immunosuppressant drugs may be given. The Food and Drug Administration (FDA) has also approved three drugs as treatments to be used after steroid therapy, including the kinase inhibitors: 

  • Jakafi® (ruxolitinib)
  • Imbruvica® (ibrutinib)
  • Rezurock® (belumosudil) 

Other treatments that may be tried include:

  • Monoclonal antibodies
  • Extracorporeal photopheresis
  • Mesenchymal stromal cells 

Graft vs. host disease survival rate

The survival rate for GVHD depends on a variety of factors, including the patient’s age, overall health and the extent of the disease.

Transplant survivorship has been increasing overall, but researchers are still examining the trends and how much impact GVHD has on mortality after transplant.

In general, lower survival rates are associated with more severe cases of GVHD, including those who have:

  • Extensive skin involvement
  • Liver or lungs affected
  • Diarrhea
  • Blood tests that indicate raised liver enzymes and low platelet levels

Two recent studies have shed some light on GVHD survival rates. A study published in July 2022 in Bone Marrow Transplantation examined data from 475 patients aged 12 years and older with acute GVHD grades 2 to 4 at multiple medical centers. Of these patients, nearly 53 percent died within seven months of onset of acute GVHD.

In a 2021 study of 937 patients in Blood Advances, researchers found that chronic GVHD was the most common cause of death not due to disease relapse, and it accounted for 22 percent of deaths at five years, and 40 percent of deaths at 12 years.

Patients who notice any GVHD symptoms should contact the care team to begin treatment as soon as possible.

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