Graft-Versus-Host Disease in Childhood Cancer
Some individuals being treated for certain cancers may undergo a Stem Cell Transplant along with Chemotherapy or Radiation Therapy. In Stem Cell Transplantation, healthy stem cells are taken either from themselves or a donor.
An allogeneic transplant is a procedure which involves using blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, cancer-free donor who matches the recipient’s tissue type. Most commonly, donors are a close relative, such as a sibling, but could also be an unrelated donor.
Using a donor for stem cell transplants offers what is called a graft-versus-cancer effect, in which the donor’s stem cells (graft) may attack any cancer cells found in the recipient (host).
Unfortunately, however, a stem cell transplant can also cause a condition called graft-versus-host-disease (GVHD).
GVHD is a serious and potentially life-threatening condition in which the donor cells attack the recipient’s healthy cells, causing a range of medical problems.
Types of Graft-Versus-Host Disease
There are two types of GVHD: acute and chronic.
It is hard to say exactly how often acute GVHD occurs, but some reports say 20 percent others say even as high as 80% of people who undergo an allogeneic transplant develop GVHD. This works out to over 5,500 people each year.
Acute GVHD is diagnosed within the first 100 days following an allogeneic stem cell transplant, most commonly occurring within the first 2-3 weeks following the procedure.
During this time, the new bone marrow begins to make new blood cells and the donor’s immune cells start to attack the recipient’s healthy cells.
Acute GVHD can affect the skin, liver, and gut causing symptoms, such as skin rashes, diarrhoea (sometimes with stomach pain and vomiting), or an increase in the liver enzymes. Some will go on to develop chronic GVHD.
Chronic GVHD most commonly occurs in people who have experienced acute GVHD. It can occur anywhere from 3 months to more than a year following a stem cell transplant. Cases of chronic GVHD can range from mild to severe and can be long-lasting and debilitating.
Chronic GVHD can lead to skin problems and hair-loss. It can also damage organs, such as the lungs and liver.
Chronic GVHD can have different effects on many parts of the body:
- Skin: Skin rashes and changes, such as drying, scaling, scarring, hardening, and darkening.
- Joints: Restricted motion due to skin scarring.
- Hair: Hair loss.
- Mouth: Ulcers may form in the lining of the mouth and the food pipe due to membrane dryness.
- Eyes: Loss of tears, redness, and irritation.
- Genitals: Vaginal dryness, stenosis.
- Lungs: Scarring and dryness.
- Liver: Liver damage and failure, jaundice.
In GHVD, white blood cells attack the new, foreign cells, which can lead to inflammation.
GVHD is an immune response to a foreign body. In the case of GVHD, the foreign body is not the donor cells but the cells of the person receiving the transplant.
Donor T cells, which are white blood cells that are responsible for fighting infection, do not recognize the host’s cells in whichever organ is affected after receiving a stem cell transplant.
Tissue damage caused by the treatment the recipient is receiving leads to the release of inflammatory proteins. These proteins increase the expression of substances within the recipient’s cells that stimulate the immune cells.
In turn, this leads to the activation of donor T cells against the cells of the recipient. The immune response is mediated by the T cells of the host. As target cells die and tissue is destroyed by the immune reaction, a greater inflammatory response occurs.
All people have a unique protein that is inherited from both parents, called human leukocyte antigen (HLA). The only people with identical HLA are identical twins. In an attempt to prevent GVHD from occurring, donors and recipients are HLA-matched before to the transfusion to be sure their HLA matches as closely as possible.
HLA-matching does not always work, however, and so there is always a risk for GVHD with allogeneic stem cell transplants.
The chances of GVHD occurring increase under some circumstances, such as when:
- The recipient is not a blood relative of the donor
- There is donor hla mismatch, even if only slight
- Donor stem cells have high t cell counts
- The donor is older in age
- The donor is of the opposite sex
- The donor is infected with cytomegalovirus (cmv), and the recipient has not been infected previously
- The recipient is receiving white blood cells from a donor
Acute GVHD typically leads to a skin rash affecting the palms of the hands, soles of the feet, ears, or face. People may experience pain or itching with these skin rashes. This rash can spread to the trunk of the body.
Other common symptoms include:
- Burning, redness of the skin
- Skin blistering and flaking
- Nausea and vomiting
- Stomach cramping
- Loss of appetite
- Stomach and intestinal bleeding
- Yellowing of the skin or whites of the eyes, indicating liver damage
- Digestive tract ulcers from mouth and throat dryness
- Lung, vaginal, and other membrane dryness
- Shortness of breath
- Weight loss
- Reduced joint mobility
- Hair loss
- Eye irritation, redness, visual changes, and loss of tear production
- Tiredness, chronic pain, and muscle weakness
Doctors will discuss in detail any symptoms that should be reported to them for immediate care and treatment.
Doctors can diagnose both acute and chronic GVHD after an evaluation of symptoms. However, a biopsy of a tissue sample will confirm the condition.
Biopsies may be taken from the skin, liver, stomach, intestine, or other sites to get an accurate diagnosis. Doctors may recommend other tests as necessary.
Healthcare providers will base a treatment plan on whether the GVHD is acute or chronic.
Healthcare providers use medications to suppress the immune system or anti-inflammatory medications such as steroids to treat GVHD. The choice will depend on the whether the condition is acute or chronic.
People with GVHD may require treatment for up to a year and beyond depending on how they respond to therapy.
Acute GVHD is typically treated with a class of medication called glucocorticoids (steroids) and cyclosporine (immunosuppressive drugs).
Additional medications that have either been newly approved or are undergoing evaluation in clinical trials 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 Non-Absorbable Corticosteroids, Such As Budesonide Or Beclomethasone Dipropionate
- Intra-Arterial Corticosteroids
- Pentostatin (Nipent)
Another potential form of treatment is extracorporeal photopheresis, a procedure under study that removes, treats, and reinfuses the patient’s blood. Infusions of mesenchymal stem cells are currently under trial.
Chronic GVHD is typically treated with a class of steroids called corticosteroids, and possibly cyclosporine. Other medications are available if the GVHD is not responding to traditional therapy. These include:
- daclizumab (Zenapax)
- infliximab (Remicade)
- mycophenolate mofetil (CellCept)
- pentostatin (Nipent)
- tacrolimus (Prograf)
- thalidomide (Thalomid)
- imatinibmesylate (Gleevec) for some skin changes
GVHD can range from mild to severe and can be life-threatening in some cases. Doctors will discuss a person’s outlook individually, basing outcomes on several factors.