What is graft-versus-host disease (GVHD)?

Definition

Graft-versus-host disease (GVHD) occurs as a complication of a bone marrow
or stem
cell
transplant when new cells are transplanted from a donor to a recipient. The tissue sample that is
taken from the donor and inserted into the recipient is called a graft. The donor
cells in the graft begin to create antibodies (proteins the immune system
produces to fight infection). These foreign antibodies attack the recipient’s
healthy cells in the digestive system, skin, and liver.

Acute GVHD can occur soon after the transplantation, usually within the first one hundred days. Chronic GVHD can occur after the first one hundred days and can flare up at different times for several years after the transplantation. A person can experience both acute and chronic GVHD or just one of the syndromes.

Causes

GVHD is an immune response generated from the newly transplanted cells from an allogeneic donor, in which samples are taken from another person, either related or unrelated to the patient. Each person’s chemical makeup is unique, and for transplantation to succeed, physicians must find donors who are similar to the recipient in chemical makeup.

Physicians look for certain proteins on blood cells called histocompatibility antigens (also known as HLA markers). These
proteins are responsible for recognizing foreign invaders and for activating the
immune
system to eliminate any potential infections that are
discovered. The HLA markers will be similar but will never be identical to the
recipient’s healthy cells, unless the donor and recipient are identical twins.

As the graft of cells begins to grow and integrate into the patient’s body, the new cells recognize these slight differences and react by attacking other healthy cells within the patient’s body, particularly cells found in the digestive tract, skin, and liver, just as a healthy immune system would attack bacteria or viruses. This process causes damage to these areas and complications for the patient.

Risk Factors

GVHD occurs only in persons who receive allogeneic grafts of peripherally
collected stem cells, bone marrow, or umbilical cord blood to treat a variety of
diseases, including certain cancers and sickle cell anemia. Umbilical cord blood
grafts have less of a risk for GVHD than the other types of grafts, and grafts
from unrelated donors have greater potential for causing GVHD than grafts from
biological family members. Other risk factors include receiving a graft from a
person of the opposite gender, older age of either the donor or the recipient,
receiving a poorly matched graft, and having a cytomegalovirus (herpes)
infection. Transplant recipients who have had their spleen removed are also at
risk for GVHD. Men experience GVHD more often than do women.

People who have acute GVHD are at risk for developing chronic GVHD. Acute GVHD
occurs in as many as 90 percent of allogeneic transplant recipients, with about 50
percent of occurrences considered to be clinically significant (that is, requiring
medical intervention). Chronic GVHD affects as many as 80 percent of
bone marrow
transplant recipients.

Symptoms

Symptoms depend upon the area of the body that is affected. The skin is usually
affected first, and the patient will usually experience burning, itching, and a
rash. The skin will darken and have a reddish tone. The hands, feet, upper back,
cheeks, neck, and ears are the most commonly affected areas. GVHD can progress to
other areas of the body and include more serious skin complications, including
blisters filled with a clear liquid. GVHD can resemble a severe burn. The most
severe form can cause tissue necrosis (progressive skin-cell
death).

When GVHD affects the liver, typical symptoms of liver disease occur, including jaundice (a yellowish tone to the skin and whites of the eyes), abdominal pain and cramping, weight gain, and an increase of fluid in the abdomen (ascites).

When GVHD includes the digestive tract, it affects the outer lining of the system (known as the mucosal lining). The most common symptom is diarrhea, which can be severe. The patient may also experience nausea and appetite loss.

The symptoms for each system can occur independently or at the same time. All three systems may be affected or only one or two. Symptoms can range from mild to life-threatening.

Screening and Diagnosis

To determine if a person has GVHD, physicians must rule out other diseases that
have similar symptoms and that often occur in people who have bone marrow or stem
cell transplants. These conditions include drug toxicity, reactions to
radiation
therapy or chemotherapy, bacterial or viral
infections, or complications from total parental nutrition (tube feeding).

Diagnostic studies will depend on the part of the body that is affected.
Because the risk is so high for GVHD in patients who receive an allogeneic stem
cell or bone marrow transplant, they are often monitored for early signs of the
disease through blood tests. Imaging scans and tissue biopsy of the affected
system are often performed to rule out GVHD in persons who are experiencing
symptoms. Endoscopy can be performed on persons who are experiencing
digestive tract symptoms.

Treatment and Therapy

The first-line treatment for GVHD involves suppressing the immune system. Steroids are
often prescribed for this. If this treatment does not work, a combination of
methotrexate and mycophenolate is prescribed. In addition,
therapies to alleviate digestive, skin, and liver symptoms also will be initiated.

Prevention and Outcomes

Suppressing the immune system is also used as an approach to GVHD prevention. In addition, finding the proper donor match is crucial to preventing GVHD. Taking steps to prevent acute GVHD will also help to prevent chronic GVHD.

Bibliography

Cancer Research U.K. “Graft Versus Host Disease.” Available at http://www.cancerhelp.org.uk/coping-with-cancer/coping-physically/gvhd.

Eggert, Julie, ed. Cancer Basics. Pittsburgh, Pa.: Oncology Nursing Society, 2010. Describes skin, liver, and digestive problems associated with different types of cancer, including acute and chronic GVHD.

Latchford, Teresa. “Cutaneous Effects of Blood and Marrow Transplantation” In Principles of Skin Care and the Oncology Patient. Pittsburgh, Pa.: Oncology Nursing Society, 2010. Provides a description and illustrations of GVHD and other skin problems associated with stem cell and marrow transplantation.

National Institutes of Health. “GVHD (Graft-Versus-Host-Disease): A Guide for Patients and Families After Stem Cell Transplant.” Available at http://www.cc.nih.gov/ccc/patient_education/pepubs/gvh.pdf.

Ruiz, Phillip, Yaxia Zhang, and Shoib Sarwar. “Graft Versus Host Disease.” Available at http://emedicine.medscape.com/article/886758-overview. A comprehensive overview of GVHD, including experimental treatments.