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If you have an allogeneic stem cell transplantation or a reduced-intensity allogeneic transplant, you're at high risk of developing graft versus host disease (GVHD). In fact, the older the person, the higher the risk for GVHD.

GVHD develops when the donor's immune cells mistakenly attack the patient's normal cells. GVHD can be mild, moderate or severe - even life threatening. Its symptoms can include:

  • rashes, which include burning and redness, that erupt on the palms or soles and may spread to the trunk and eventually to the entire body
  • blistering, causing the exposed skin surface to flake off in severe cases
  • nausea, vomiting, abdominal cramps, diarrhea and loss of appetite, which can indicate that the gastrointestinal (digestive) tract is affected
  • jaundice, or a yellowing of the skin, which can indicate that your liver is damaged
  • excessive dryness of the mouth and throat, leading to ulcers
  • dryness of the lungs, vagina and other surfaces

GVHD can be acute or chronic. Its severity depends on the differences in tissue type between patient and donor. The older the patient, the more frequent and serious the reaction may be.

Preventing GVHD

One to two days before your stem cell infusion, you'll take drugs to help prevent GVHD. Regimens include:

  • cyclosporine and methotrexate
  • tacrolimus (Prograf®) and methotrexate
  • tacrolimus and mycophenolate mofetil (CellCept®)
  • Prograf and sirolimus (Rapamune®)

These regimens suppress the immune system. You may need to continue to take them for many months after transplantation.

To diagnose GVHD, your doctor will likely biopsy one of your affected organs. He or she will give GVHD a grade from I (mildest) to IV (most severe).

Acute GVHD

Acute GVHD can occur soon after the transplanted cells begin to appear in the recipient. Acute GVHD can be mild, moderate or severe. It may be a life-threatening condition if its manifestations are difficult to control.

Chronic GVHD

Chronic GVHD usually occurs at about three months post-transplant but may not develop for a year or more after the transplant. It's more likely to occur in patients who previously have had acute GVHD, but it may appear without prior acute GVHD.

Chronic GVHD can be mild (with later improvement) or more severe, persistent and incapacitating. Most patients with chronic GVHD experience skin problems that may start with a rash and itching and the skin may become scaly. As the reaction becomes more severe, so do the symptoms, which may include one or more of the following:

  • Patches of skin may be lost.
  • Skin color may deepen and texture may become hard.
  • The skin may heal by scarring, causing the motion of nearby joints, such as the fingers, to become restricted.
  • Hair loss may accompany skin injury.
  • The drying and scarring effects of the attack by the donor cells can affect the inside of the mouth and the esophagus (from the throat to the stomach), causing them to become excessively dry and damaged. This reaction can result in ulcers.
  • The tendency to drying can lead to loss of tear formation and general eye redness and irritation. Dryness of the vagina and other surfaces may also occur.
  • The lungs may also show effects of drying and scarring.
  • Liver injury can result in liver failure and diminished bile flow.
  • Bile may back up into the blood and cause jaundice.

In some cases, internal organ damage may not be immediately obvious, but they can be detected by blood chemistry measurements.

GVHD Treatment

Several drugs have been developed to prevent or lessen GVHD. These drugs, when combined with early detection and advances in understanding the disease, have resulted in significant reductions in serious or fatal outcomes from GVHD. However, GVHD doesn't always respond to these treatments and can sometimes result in fatal outcomes. Many deaths related to GVHD occur because of infections that develop in patients with suppressed immune systems.

Several advances in transplantation techniques have helped to reduce the risk of developing acute GVHD:

  • more precise HLA tissue matching
  • immunosuppressive drugs
  • depletion of T lymphocytes from the donor graft
  • the use of umbilical cord blood as the source of donor cells

Types of Drugs Used to Treat GVHD

Glucocorticoids such as methylprednisolone or prednisone combined with cyclosporine are used to treat acute GVDH. New drugs and strategies available now or in clinical trials can supplement standard treatment. They include:

  • antithymocyte globulin (rabbit ATG; Thymoglobulin®)
  • denileukin diftitox (Ontak®)
  • monoclonal antibodies such as daclizumab (Zenapax®); infliximab (Remicade®); or, more rarely, alemtuzumab (Campath®)
  • mycophenolate mofetil (CellCept®)
  • sirolimus (Rapamune®)
  • tacrolimus (Prograf®)
  • oral nonabsorbable corticosteroids such as budesonide or beclomethasone dipropionate
  • intra-arterial corticosteroids
  • pentostatin (Nipent®)
  • extracorporeal photopheresis (a procedure under study that removes, treats and reinfuses the patient's blood)
  • infusions of mesenchymal stem cells (experimental only)

Corticosteroids are the primary therapy used for chronic GVHD. Cyclosporine may be combined with prednisone. Clinical trials investigating GVHD that doesn't respond to steroid treatment have reported some success for the following treatments:

  • daclizumab (Zenapax®)
  • etanercept (Enbrel®)
  • extracorporeal photopheresis
  • infliximab (Remicade®)
  • mycophenolate mofetil (CellCept®)
  • pentostatin (Nipent®)
  • rituximab (Rituxan®; experimental only)
  • tacrolimus (Prograf®)
  • thalidomide (Thalomid®)
  • imatinib mesylate (Gleevec®) for some skin changes

Supportive Care

Patients must pay attention to nutrition and take supportive care measures for their skin, eyes, mouth, vaginal mucosa and lungs. Because both the disease and its treatments suppress the immune system, it's important that your doctor monitors you for and treats infections. If GVHD stabilizes or improves, your doctor may taper drug dosages or eventually stop medications for GVHD.

Usually after a year or so, your body will form new T lymphocytes from the engrafted donor cells. The newly formed lymphocytes won't attack your cells, and immunosuppressive therapy can be stopped. Your immune system can work efficiently to protect against infections, and your risk of infection begins to approach that of a healthy person. This "state of tolerance" between the donor immune cells and your cells is important for long-term transplant success.

More to Explore

Download or order The Leukemia & Lymphoma Society's free booklet Blood and Marrow Stem Cell Transplantation

last updated on Tuesday, March 15, 2011

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