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Graft Versus Host Disease (GVHD)

What is Graft Versus Host Disease?

Graft versus host disease (GVHD) is a serious, sometimes life-threatening complication of a hematopoietic cell transplant (commonly known as bone marrow transplant or stem cell transplant).

GVHD can happen after an allogeneic transplant. There are 2 kinds of transplants based on the source of the hematopoietic (blood-forming) cells – allogeneic and autologous. An allogeneic transplant occurs when the cells come from another person. An autologous transplant occurs when the cells come from the patient.

GVHD occurs when immune cells from the donor (the graft) recognize the patient’s normal cells and tissues (the host) as foreign and attack them. The immune reaction symptoms depend on which part of the body is damaged by the donor cells.

GVHD occurs in approximately 20-50% of patients after transplant. It can develop at any time after transplant. Once it occurs, GVHD can be difficult to treat and in severe cases can be life-threatening.

GVHD has 2 types:

  • Acute
  • Chronic

Acute GVHD

Acute GVHD is commonly defined as disease that occurs during the first 100 days after transplant. But it can occur at any time. Signs and symptoms typically involve the skin, gastrointestinal (GI) tract, and liver. The donor immune cells involved are primarily T cells.

Signs and Symptoms of Acute GVHD

Signs and symptoms may be mild to severe. They may include:

Skin

  • Rash
  • Redness
  • Blisters
  • Ulcers

GI tract

  • Nausea
  • Vomiting
  • Loss of appetite
  • Watery or bloody diarrhea
  • Abdominal pain
  • Low albumin levels
  • Jaundice

Liver

  • Increased bilirubin levels
  • Liver problems

Chronic GVHD

Chronic GVHD is commonly defined as disease that occurs more than 100 days after transplant. But it can appear earlier. It is similar to an autoimmune disease and can affect multiple organs or organ systems. The donor immune response involves primarily T cells and B cells.

Signs and Symptoms of Chronic GVHD

Signs and symptoms may be mild to severe. They may include:

  • Skin symptoms — Rash and itching, scaly skin, lost patches of skin, darkening of skin, hardening of skin texture, scarring that can cause the motion of nearby joints, such as fingers, to become restricted
  • Nail damage or loss
  • Hair loss
  • Joint stiffness
  • Dryness and sores in the mouth and esophagus
  • Dry eyes and redness in the eyes
  • Females - Dryness of the vagina and other surfaces
  • Males – Shortening, changes in the penis
  • Cough, shortness of breath, wheezing
  • Drying and scarring of lungs
  • Liver injury or liver failure
  • Jaundice

Risk Factors

Risk factors for GVHD include

  • Degree of “mismatch” between donor and patient (HLA-match)

Transplant donors may either be siblings, other family members, or people in the National Donor Marrow Registry who are unrelated to the patient.

When considering the best possible donor, the care team looks for the closest HLA match. HLA stands for human leukocyte antigens. HLA are proteins or markers that are on most cells in the body. The immune system uses HLA to recognize which cells belong in your body and which ones don’t.

There are many HLA markers. Half are inherited from your mother and half from your father. Each brother or sister who has the same parents has a 25% chance (1 in 4) of being a close HLA match. Other family members have a slim chance of being close HLA matches. About 70% of patients who need a transplant won’t have a fully matched donor in their family.

A patient whose donor is a close match has a lower chance of developing GVHD than someone whose donor is not as closely matched.

  • Age of donor and recipient

Research studies have shown that cells from younger donors bring about better long-term survival for transplant patients. Doctors request donors in the 18-44 age group 85% of the time. The National Donor Marrow Registry includes donors between 18 and 60.

  • Source of hematopoietic (blood-forming) cells

Some studies show there is higher risk of GVHD when there are a lot of T cells in the graft.

  • Intensity of conditioning regimen

Some studies show risk is lowered with reduced-intensity chemotherapy compared to more intensive regimen.

Prevention

The care team will take steps to help prevent GVHD.

  • Donor selection — The care team will select the closest HLA-matched donor available.
  • Donor cell manipulation — The donor cells (graft) may be manipulated to lessen the number of donor T cells, in an attempt to prevent the donor immune reaction that causes GVHD. This manipulation may occur in a cell processing facility before the cells are given to the patient or by giving the patient certain medications after the cells are given.
  • Immunosuppressive medications — Patients may receive medications to decrease donor immune cell activity. Commonly used medications include cyclosporine, tacrolimus, sirolimus, methotrexate, mycophenolate mofetil, cyclophosphamide, anti-thymocyte globulin (ATG) and alemtuzumab.

What Patients and Families Can Do

Patients and families are encouraged to take an active role in helping to prevent GVHD:

  • Follow medication instructions as directed. It is crucial that patients take medications exactly as prescribed by the care team.
  • Watch for early signs and symptoms. Alert care team to any changes. These changes may indicate GVHD. In general, GVHD is more treatable in early stages. Catching it quickly can make a positive difference in the patient’s long-term health.
  • Protect skin against the sun. Sun exposure can trigger GVHD or make it worse. When patients go outside, they are encouraged to wear a hat, long sleeves, long pants, and sunscreen with an SPF of 30 or higher. The best protection is to avoid being out in the sun.

Diagnosis and Monitoring

Patients will be monitored very closely for signs of GVHD. This process may include physical exams, taking of medical history, lab tests, and imaging tests.

Further testing depends of types of symptoms. Tests could include obtaining a tissue sample through a biopsy, including skin, upper endoscopy and/or colonoscopy, lab tests, and imaging tests.

Treatment

Treatment is aimed at stopping the overactive donor immune response and retraining the immune system to not attack the normal host tissues. Treatment may vary between patients based on their symptoms.

Medications

Corticosteroids such as methylprednisolone, dexamethasone and prednisone are a mainstay of treatment for GVHD. Medications may be given by vein, mouth, cream or ointment, eye drops or oral rinse.

Other medicines may include immunosuppressive medications (such as those listed above in Prevention section), immunotherapy and targeted therapy.

Light therapy

Narrowband ultraviolet (UV) B phototherapy and extracorporeal photopheresis (ECP) are 2 therapies that both use light to treat GVHD. 

UV phototherapy uses UVB radiation to heal skin problems caused by GVHD. 

ECP involves collecting blood and separating it into red blood cells, white blood cells, and platelets. The white blood cells are treated with drugs and exposed to ultraviolet (UV) light. Then these cells, along with the other blood cells, are returned to the body. The treated cells may stimulate the immune system to help fight GVHD.

Note: A common misconception is that GVHD is necessary for a transplant to be successful. This is not true. A patient does not have to develop GVHD for the transplant to be successful.

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