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- Risks and Complications
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Graft-versus-host disease (GVHD) facts
- Graft-versus-host disease (GVHD) is an immune condition that occurs in a patient after transplantation when immune cells present in donor tissue (the graft) attack the host's own tissues.
- GVHD is a complication after bone marrow transplantation (stem cell transplants) from both related and unrelated donors. These types of transplants are called allogeneic transplants.
- With acute GVHD and chronic GVHD, symptoms can range from mild to severe and life-threatening and often include skin inflammation, jaundice, and GI discomfort along with other organ problems.
- Acute GVHD usually occurs within the first 100 days post-transplant; the acute form of the disease causes clinical symptoms of skin rash, liver problems, and intestinal symptoms like nausea and diarrhea.
- Chronic GVHD occurs later; the chronic form of the disease may affect a number of different organs and body systems.
- GVHD has a complex pathophysiology that involves a number of interactions between the immune cells of the transplant donor and recipient patient.
- Neither acute nor chronic GVHD can be prevented, although there are measures to help reduce the risk.
- Immunosuppressive medications are the primary therapy for patients with GVHD, including both corticosteroids and other immune-suppressing drugs.
- A skin biopsy is often performed to establish the diagnosis of GVHD in a patient with signs and symptoms of the condition.
- Chronic GVHD is more likely to occur in those who experienced the acute form, but it may also occur in those who never had acute GVHD.
- Advances in transplant technology are ongoing with the goal of decreasing the incidence of GVHD, including the use of cyclosporine, methotrexate, and other preventive medications; nevertheless, it is not possible at this time to prevent all cases of GVHD.
What is graft-versus-host disease?
Graft-versus-host disease (GVHD) is an immune condition that occurs after transplant procedures when immune cells from the donor (known as the graft or graft cells) attack the recipient patient host's tissues; the disease is a side effect that is common after an allogeneic bone marrow transplant (stem cell transplant). An allogeneic transplant is one in which a patient receives bone marrow tissue or cells from a donor. Stem cell transplantation is a common treatment for many different cancers (malignancies), including cancers that affect the blood and lymph nodes, as well as some other (non-cancer) conditions that affect the blood or immune system. A stem cell transplant is sometimes performed after a relapse of leukemia or lymphoma that occurs after initial treatment. In addition to bone marrow transplant procedures, GVHD can also occur after transplantation of solid organs that may contain immune system cells such as white blood cells.
Tissues from healthy donors are checked prior to bone marrow transplant to see how closely matched they are to the host's own cells. When there is a close match in certain genetic markers, the risk of the disease is lower. The disease can range from mild to life-threatening in severity. There are two types of GVHD: acute GVHD and chronic GVHD.
The chance of developing GVHD is around 30%-40% when the donor and recipient are related and around 60%-80% when the donor and recipient are not related. The disease can affect many different organs in the body.
What causes graft-versus-host disease?
The pathophysiology of graft versus host disease is complex. GVHD is the result of a series of complex interactions between the immune cells of the donor (the graft) and the host tissues; the disease is most likely to occur after a transplantation procedure when donor and recipient tissues are not genetically similar. A number of cytokines and other immune signaling compounds are believed to be important in the development of the condition.
What are risk factors for GVHD?
Patients undergoing bone marrow transplant (stem cell transplant) from a donor are at increased risk for GVHD. Medical research has also shown that the likelihood of developing GVHD increases with certain underlying disease states. The disease is also more likely to occur in older people. The risk is slightly elevated when the donor and patient are of different gender. Before the transplanted cells are given to the patient, a pretreatment regimen of drugs is given to suppress the immune system and to help prevent GVHD. Other risk factors for the disease include having a tissue donor who has been pregnant and advanced age of either the donor or recipient.
What are graft-versus-host disease symptoms and signs? What are the types of GVHD?
There are two main types of GVHD: acute GVHD and chronic GVHD.
Acute GVHD typically occurs within 100 days after the stem cell transplantation. "Acute" is a medical term that means that a condition appears early or suddenly, while "chronic" refers to a condition that develops over time. Acute graft-versus-host disease usually involves a distinct set of clinical symptoms and signs that include the following:
- Dermatitis, or skin inflammation, is characterized by an itchy, red, and possibly painful rash.
- Hepatitis, or liver inflammation, may not have symptoms at the outset but can also lead to jaundice (yellowing of the skin and whites of the eyes) and other signs of liver failure.
- Enteritis, or inflammation of the intestinal tract, can lead to diarrhea, nausea, vomiting, cramping, abdominal pain, or blood in the stool. The diarrhea of acute GVHD has been described as greenish, watery, mucoid or having mucus, and/or containing sloughed intestinal lining cells that may appears as casts (lumps or clumps of cells) in the stool.
Chronic GVHD usually begins after the first 100 days following a transplant. Chronic graft-versus-host disease is more likely to occur in patients who experienced the acute form of the disease, but it can also develop on its own in someone who never has had GVHD before.
- Dry eyes or mouth
- Vision changes
- White patches inside the mouth or mouth ulcers
- Difficulty swallowing
- Hair loss
- Sensitivity to spicy or acidic foods
- Mouth pain
- Pulmonary symptoms include wheezing or shortness of breath
- Muscle or joint pain and weakness
- Skin rash that is red to purple, flat or raised, and may be accompanied by thickened skin and raised areas of skin
- Skin discoloration
- Vaginal dryness
- Loss of appetite and weight loss
- Jaundice, or yellowing of the skin and whites of the eyes
- Abdominal pain or tenderness
The symptoms of both acute and chronic GVHD may be staged as mild, moderate, or severe enough to be life-threatening. Some patients may develop other types of GVHD:
- Persistent, recurrent, late-onset GVHD: Patients develop acute GVHD symptoms more than 100 days post-transplant.
- Overlap syndrome: anytime when post transplant patients develop symptoms of both acute and chronic GVHD
What specialists treat GVHD?
Patients with GVHD are treated by the team of medical specialists that manage the transplantation process. Hematologist-oncologists (medical doctors specializing in the treatment of cancerous tumors and blood diseases) who are transplant specialists typically lead these teams and coordinate the patient's care.
What tests do health care professionals use to diagnose GVHD?
A tissue biopsy (a small sample of tissue removed for examination under a microscope by a pathologist physician) is a common test used to diagnose GVHD when the patient's clinical signs and symptoms suggest that GVHD is present. Sometimes, biopsies from other sites in the body are done instead of or in addition to the skin biopsy.
Blood tests that can be helpful in managing the patient with GVHD include blood cell counts and blood chemistry profiles. Blood tests that assess liver function are also commonly performed when GVHD is suspected or diagnosed.
What are GVHD treatment options?
Immunosuppressant medications are the hallmark of treatment for GVHD. These include both corticosteroid drugs (such as prednisolone or methylprednisolone) and more advanced medications and techniques that reduce the immune response. Corticosteroids are the mainstay of therapy for GVHD, but other medications may be added or given when the GVHD does not respond well to steroid treatment. A number of different medications and combinations of medications are available to treat GVHD, and clinical trials are ongoing to examine new treatments as well as treatments for GVHD that does not respond to steroid treatment.
Some nonsteroid immune-suppressing drugs and treatments that have been used to treat GVHD include the following:
- Antithymocyte globulin (Thymoglobulin)
- Denileukin diftitox (Ontak)
- Daclizumab (Zenapax)
- Infliximab (Remicade)
- Sirolimus (Rapamune)
- Tacrolimus (Prograf)
- Mycophenolate mofetil (CellCept)
- Etanercept (Enbrel)
- Pentostatin (Nipent)
- Thalidomide (Thalomid)
An increased risk of infections, including bacterial and fungal infections, is the main health risk and side effect of treatment with immune-suppressing drugs.
Extracorporeal photophoresis (ECP) is a treatment that involves a combination of leukopheresis and photodynamic therapy, in which patient blood is exposed to a sensitizing agent followed by ultraviolet A irradiation and reinfused into the patient.
What is the prognosis of graft-versus-host disease?
The prognosis or outcome of GVHD depends both upon the severity and extent of the symptoms and the effectiveness of treatment. GVHD is highly variable, with symptoms that can range from mild to life-threatening. Signs and symptoms of chronic GVHD may last for years or may be permanent in some people.
Is it possible to prevent GVHD?
Advances in medical transplantation techniques have helped to reduce the risk of developing acute GVHD, including more precise techniques to determine whether donor cells are a good match for the recipient and processing of the donor cells to remove T cells, or T lymphocytes; a T cell is a type of immune cell that mediates the reaction in GVHD. Using umbilical cord blood as a source of donor cells can also reduce the likelihood of developing GVHD. Finally, patients undergoing stem cell transplants are given a regimen of immune-suppressing drugs such as cyclosporine, methotrexate, tacrolimus (Prograf), mycophenolate mofetil (Cellcept), or sirolimus (Rapamune) to decrease the likelihood of developing the condition. Even with advancing technology, it is not always possible to prevent GVHD.
Mandanas, Romeo A. "Graft Versus Host Disease." Medscape.com. Dec. 11, 2017. <http://emedicine.medscape.com/article/429037-overview>.
Shernan, G., Holtan, Marcelo Pasquini, and Daniel J. Weisdorf. "Acute graft-versus-host disease: a bench-to-bedside update." Blood 124 (2014): 363-373.
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