Graft-versus-host disease (GVHD)
Graft-versus-host disease (GVHD) is a serious complication that can arise following bone marrow or stem cell transplants, wherein donor cells (the graft) attack the recipient's healthy tissues. This immune response is triggered by the recognition of minor differences in histocompatibility antigens between the donor and the recipient, prompting the new cells to target healthy cells, primarily affecting the skin, liver, and gastrointestinal system. GVHD is classified into acute and chronic forms, with acute GVHD typically occurring within the first 100 days post-transplant, while chronic GVHD can develop later and may persist for years.
Risk factors for developing GVHD include receiving grafts from unrelated donors, age, gender differences between donor and recipient, and prior infections such as cytomegalovirus. Symptoms can vary widely and may range from mild skin rashes and digestive issues to severe liver dysfunction and systemic complications. Diagnosis involves ruling out other conditions with similar symptoms, and monitoring is crucial for early detection. Treatment primarily focuses on immunosuppression using medications like steroids, with additional therapies aimed at alleviating specific symptoms. Preventive measures emphasize the importance of finding an appropriate donor match to reduce the risk of GVHD.
Graft-versus-host disease (GVHD)
- ANATOMY OR SYSTEM AFFECTED: Blood, bones, gastrointestinal system, immune system, liver, musculoskeletal system, skin, tissue
Definition
Graft-versus-host disease (GVHD) occurs as a complication of a bone marrow transplant or stem cell transplant when new cells are transplanted from a donor to a recipient. The tissue sample 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 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 never 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 various 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 women.
People who have acute GVHD are at risk for developing chronic GVHD. Acute GVHD occurs in between 30 and 70 percent of allogeneic transplant recipients, with between 10 and 50 percent of occurrences considered to be clinically significant (that is, requiring medical intervention). Chronic GVHD affects aroun 40 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 ascites, an increase of fluid in the abdomen.
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 with similar symptoms that often occur in people with 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 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, ruxolitinib, ibrutinib, or belumosudil 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.
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