Graft-versus-host disease (GVHD) and cancer
Graft-versus-host disease (GVHD) is a significant complication that may arise following allogeneic bone marrow or umbilical cord blood transplants. In this condition, immune cells from the donor (the "graft") recognize the recipient's cells (the "host") as foreign and launch an immune attack. This response can be influenced by various risk factors, such as age, prior medical treatments, and the compatibility of donor and recipient cells. GVHD manifests in two forms: acute, which typically occurs within the first 100 days post-transplant, and chronic, which can develop later and persist for years.
Symptoms of GVHD vary depending on the affected organs and may include skin rashes, gastrointestinal issues, and liver dysfunction. Early diagnosis is crucial for effective management, which often involves corticosteroids and other immunosuppressive therapies. The incidence of GVHD can range significantly based on factors like HLA matching and the type of transplant. While severe GVHD can lead to serious complications, the presence of chronic GVHD may sometimes correlate with improved long-term survival. Preventive measures include careful donor matching and specific drug regimens to minimize the risk of GVHD.
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Graft-versus-host disease (GVHD) and cancer
RELATED CONDITIONS: Bone marrow transplantation, stem cell transplantation, allogeneic transplant
DEFINITION: Following an allogeneic bone marrow transplant or umbilical cord blood transplant, graft-versus-host disease (GVHD) may develop. GVHD is a complication that occurs when white blood cells (or immune cells, also known as T cells) from the donor or cord blood, administered to the patient during the transplant, attack the patient’s own cells as foreign. The donor cells are called the “graft,” and the patient’s body is considered the “host,” hence the name graft-versus-host disease.
Risk factors: Those who have undergone an allogeneic bone marrow transplant or an umbilical cord blood transplant are at risk for this condition. Older patients, those who have had a splenectomy, or if pre-transplant treatment is reduced, the patient is more likely to develop the disease. Additionally, if the donor is a different sex than the host, has been pregnant, has cytomegalovirus, is older, or is not a perfect match for the host, the recipient is more likely to develop GVHD.
Etiology and the disease process: When patients have an allogeneic bone marrow transplant, they receive stem cells from a relative, usually a parent, sister, or brother. An unrelated person’s stem cells may also be used if the donor’s cells match the patient’s. Umbilical cord blood, collected from the umbilical cord and placenta at the birth of a baby and stored in a cord blood bank, is rich in stem cells and may be used if a match to the patient is found. The transplant’s success is often related to how well the proteins on the surface of the donated cells match the patient's cells. These proteins are called human leukocyte-associated (HLA) antigens and are identified by a blood test. Acute GVHD can develop within a few weeks of the transplant but always within the first one hundred days after the transplant. Patients who get acute GVHD are more likely to develop chronic GVHD. Chronic GVHD develops well after the transplant, usually during or after the third-month post-transplant in patients who may have developed acute GVHD. Chronic GVHD can last for years after the transplant and, like acute GVHD, can be mild to life-threatening.
Incidence: The incidence rate of acute GVHD varies from 33 percent in HLA identical siblings to 75 percent in unrelated, HLA-matched, or related, partially matched transplants. Chronic GVHD may occur in one-third to two-thirds of transplant patients. Incidence rates vary with the initial use and aggressiveness of immunosuppressive therapy and the use of T-cell-depleted stem cells. Incidence is generally lower in patients receiving matched cord blood.
Symptoms: Symptoms of GVHD depend on the part of the body affected by the disease. The skin, eyes, stomach, intestines, and liver are the most commonly affected organs in the body. In acute GVHD, skin symptoms include the development of a rash on the palms of the hands and soles of the feet. If GVHD is severe, blisters may appear. Cramping, nausea, and diarrhea may occur with digestive tract involvement, and jaundice (yellowing of the skin) may occur with liver involvement. Chronic GVHD symptoms include skin changes, including rash, pain in the mouth, dry mouth and eyes, and digestive tract symptoms. Advanced chronic GVHD may cause a hardening or tightness in the skin, and joints may become stiff.
Screening and diagnosis: Screening and diagnosis are made based on symptoms occurring after transplant, including fever, rashes, and organ involvement. A definitive diagnosis is made by skin or organ biopsy. There are four stages of acute GVHD, with rankings based on skin, liver, and gastrointestinal changes. Five grades are given to the acute version, ranging from none to life-threatening. A higher stage and grade means a more aggressive, acute GVHD. Chronic GVHD is based on a grading related to skin involvement and liver function. An early diagnosis may provide a better chance for treatment.
Treatment and therapy: Because up to 75 percent of patients may develop acute GVHD, early diagnosis is critical so that treatment may begin promptly. The initial treatment is steroids for both acute and chronic GVHD. Prednisone, cyclosporine, and intervenous methylprednisolone are the usual drugs of choice, along with symptom management. Chronic GVHD is usually treated with steroids every other day.
Calcineurin inhibitors like Tacrolimus and Cyclosporin and purine analogs like Mycophenolate mofetil may also be used to treat GVHD. Additional treatment manages the symptoms of GVHD, such as diarrhea and fever.
Prognosis, prevention, and outcomes: The development of higher-stage, acute GVHD is linked to increased morbidity and mortality. Chronic GVHD may be associated with longer-term survival, as the presence of chronic GVHD may protect a patient from relapse. Prevention includes drug prophylaxis with corticosteroids and, in some cases, methotrexate and other drugs or agents; more accurate HLA typing with as strong a match as possible; and depletion of T cells before administration of the donor cells. Using umbilical cord blood may also be preventive for GVHD, as the stem cells are immature and less likely to cause GVHD. The disease can range from very mild to life-threatening.
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