Graft-versus-host disease

Antibodies — Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy substances containing antigens.

Also known as: GVHD

Definition

Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body.

Causes, incidence, and risk factors

GVHD occurs in a bone marrow or stem cell transplant involving a donor and a recipient. The bone marrow is the soft tissue inside bones that helps form blood cells, including white cells that are responsible for the immune response. Stem cells are normall found inside bone marrow.

Since only identical twins have identical tissue types, a donor's bone marrow is normally a close, but not perfect, match to the recipient's tissues. See: Histocompatibility antigen test

The differences between the donor's cells and recipient's tissues often cause T cells (a type of white blood cells) from the donor to recognize the recipient's body tissues as foreign. When this happens, the newly transplanted cells attack the transplant recipient's body.

Acute GVHD usually happens within the first 3 months after transplant. Chronic GVHD usually starts more than 3 months after transplant, and can last a lifetime.

Rates of GVHD vary from between 30 - 40% among related donors and recipients to 60 - 80% between unrelated donors and recipients. The greater the mismatch between donor and recipient, the greater the risk of GVHD. After a transplant, the recipient usually takes drugs that suppress the immune system, which helps reduce the chances (or severity) of GVHD.

Symptoms

Symptoms in both acute and chronic GVHD range from mild to severe.

Common acute symptoms include:

Abdominal pain or cramps
Diarrhea
Fever
Jaundice
Skin rash
Vomiting
Weight loss

Chronic symptoms may include:

Dry eyes and dry mouth
Hair loss
Hepatitis
Lung and digestive tract disorders
Skin rash
Skin thickening

In both acute and chronic GVHD, the patient is very vulnerable to infections.

Signs and tests

The tests done usually depend on the symptoms, but may include:

Gastrointestinal endoscopy, with or without a biopsy
Liver function tests (AST, ALP, and bilirubin levels will be increased)
Liver biopsy (if the patient only has liver symptoms)
Lung x-rays
Skin biopsy

Treatment

The goal of treatment is to suppress the immune response without damaging the new cells. Medicines commonly used include methotrexate, cyclosporine, tacrolimus, sirolimus, ATG, and alemtuzumab either alone or in combination.

High-dose corticosteroids are the most effective treatment for acute GVHD. Antibodies to T cells and other medicines are given to patients who do not respond to steroids.

Treatment of chronic GVHD includes prednisone (a steroid) with or without cyclosporine. Other treatments include mycophenolate mofetil (CellCept), sirolimus (Rapamycin), and tacrolimus (Prograf).

Expectations (prognosis)

How well a person does depends on the severity of the condition. Some cases of GVHD can lead to death.

Many cases, whether acute or chronic, can be treated successfully. Sometimes treatment of the condition can lead to severe complications.

Successful treatment of GVHD does not guarantee that the transplant itself will succeed in treating the original disease.

Complications

Cholestasis
Death
Moderate to severe damage to the liver, lung, or digestive tract
Severe infection
Severe lung disease

Calling your health care provider

If you have had a bone marrow or stem cell transplant, call your health care provider immediately if any unusual symptoms appear, including:

Diarrhea
Difficulty breathing
Skin rash
Stomach cramps
Yellowing of the skin or eyes (jaundice)

Prevention

Before a transplant, your blood type and tissue type will be carefully matched with eligible donors. This matching will reduce the risk of GVHD. Whenever possible, donations from closely matched family members can further decrease the risk of this problem. Absolute prevention of GVHD is not possible, and it is a risk when receiving a transplant from anyone else.

References

Hoffman R, Benz EJ, Shattil SS, et al, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2008.

Sykes M. Transplantation immunology. In Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 46.

Review date:: June 2, 2010
Reviewed by:: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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