Stem cell or bone marrow transplants are often the best form of treatment for patients with certain diseases and blood disorders. Transplant patients always run the risk of rejecting the donated tissue, and preventative measures are taken to avoid this. Another complication that may occur in these procedures is the tendency of the newly transplanted donor tissue or cells attacking the body of the transplant recipient. This is known as graft-versus-host disease (GvHD).
Definition & Facts
Graft-versus-host disease occurs when transplanted donor cells treat the transplant recipient’s body as a foreign object and attacks it. Patients who are at risk include those undergoing an allogeneic stem cell transplant or a reduced-intensity allogeneic transplant. GvHD is categorized into two types:
- Acute graft-versus-host disease. This occurs in approximately half of all transplant recipients. This type may be mild, moderate or severe and usually appears very soon after the transplant is complete. Acute GvHD may become fatal if not controlled quickly. It typically affects the skin, liver, and gastrointestinal tract.
- Chronic graft-versus-host disease. This type of GvHD usually appears months after the transplant and most commonly appears in patients who were previously diagnosed with acute GvHD. Symptoms generally start mild and increase over time. Survival rates decrease for those with chronic graft-versus-host disease and almost any organ or organ system can be affected.
Symptoms & Complaints
- Skin rash and/or blistering of the skin. Skin rash or blistering usually begins on the palms and soles of the feet and spreads to the trunk and remainder of the body. In some cases, the entire exposed layer of skin may flake away, or skin may harden due to scarring.
- Digestive complications. Gastrointestinal problems such as nausea, vomiting, diarrhea, abdominal cramps, and loss of appetite may occur.
- Yellowing of the skin, fingernails and eyes (jaundice) is common among patients with GvHD that involves the liver.
- Dry mouth and the formation of mouth ulcers and ulcers of the throat.
- Damage to the vaginal and lung mucosa.
- Drying of mucous membranes such as sinus passages, throat, esophagus, eyes and mouth, preventing the formation of tears and saliva.
- Hair loss
- Bile backup in the blood due to liver damage.
The primary risk factor for graft-versus-host disease is a transplant patient who has previously been diagnosed with acute or chronic GvHD. This is common among patients who require more than one transplant over their lifetime.
Other primary risk factors include cases in which the donor and recipient are not similar in age or are of the opposite sex. Another common cause is a donor who has been pregnant within the last year. These factors are taken into consideration when choosing a suitable donor, but often times when a transplant is a last resort, a less than ideal donor may be used as long as they are closely matched otherwise.
While each case is different in what is the actual cause, three criteria must exist for the development of graft-versus-host disease. These three factors are known as the Billingham's criteria.
- Viable and functional immune cells extracted from immune-competent tissue is grafted in place.
- The host appears as though it is foreign to the graft
- The host’s immune system is compromised and cannot fight the attacking cells on its own.
Diagnosis & Tests
The diagnosis process begins by watching closely for visible signs of graft-versus-host disease. A physical examination will take place which can assess many common physical symptoms. Blood tests are performed to measure the amount of white blood cells in the blood. Further testing is determined by the affected organs exhibiting symptoms.
In cases in which the skin is affected, biomarkers such as elafin found in the skin can help determine the cause of GvHD. A biopsy of the skin is performed to assess this. Patients exhibiting gastrointestinal complications such as cramping, sloughing of the mucosal membrane, nausea and diarrhea will undergo an intestinal biopsy to check for GvHD.
Possible GvHD of the liver is diagnosed by testing the concentration of bilirubin in the blood in patients with acute graft-versus-host disease. Liver biopsies may also be performed to assess liver damage.
Treatment & Therapy
Treatment for graft-versus-host disease depends on what level the case is classified. The first line of defense in treating GvHD is the use of corticosteroids, prednisone, or a combination of both. Administration of steroids are started at a level 2, and the treatment is effective in approximately 35% of cases. However, this does not come without consequences. Long-term use of steroids commonly causes bone damage, diabetes mellitus, and obesity.
In cases that do not respond well to steroid therapy, there has been some success with clinical trials using immunosuppressive drugs such as etanercept. This drug is normally used for rheumatoid arthritis, and works by suppressing the protein tumor necrosis factor alpha (TNF-A.) This protein causes fevers when the immune system is inflamed, and suppressing it helps to slow the progression of GvHD.
Other clinical trials similar to this include daclizumab, extracorporeal photopheresis, infliximab, rituximab, and imatinib. Treatment is continued for several months to a year, after which the recipient’s body typically forms its own T-lymphocytes from the donor cells and rejection should subside. During this time the patient will use supportive measures such as avoiding infections, and measures to treat problems and symptoms within the skin, eyes, mouth, vaginal mucosa and the lungs.
Prevention & Prophylaxis
- Methotrexate and tacrolimus
- Methotrexate and cyclosporine
- Mycophenolate mofetil and tacrolimus
- Sirolimus and tacrolimus
Other important preventative measures include a very precise HLA tissue matching, and depletion of T-lymphocytes from donor grafts. For best results, a recipient’s own tissue should be used whenever possible, such as umbilical cord blood.
No matter the donor circumstances, the most important factor is close monitoring the patient and getting the GvHD under control as quickly as possible. This is essential in ensuring the most positive prognosis possible.