Graft-versus-host disease (GvHD) is a complication that may occur during the post-transplant period in children who receive marrow stem cells from relatives including histocompatible (HLA) matched siblings and parents, as well as those who receive marrow from unrelated donors.

GvHD reactions can occur when cells of the donor's immune system, called T lymphocytes, are infused via a blood or platelet transfusion or a bone marrow transplant into the recipient, who has received conditioning therapy. Blood and platelets are irradiated to prevent GvHD, but the donor graft cannot be treated this way since irradiation also would kill the normal bone marrow stem cells.

Types and Manifestations

GvHD can take two forms, acute and chronic:

  • Acute GvHD usually develops within three months of the transplant and occurs in 20 percent to 25 percent of HLA-matched sibling transplants in children and 30 percent to 35 percent in adults. Acute GvHD is more common in patients undergoing unrelated transplants, in particular if there is an HLA-mismatch.
  • Chronic GvHD usually develops three to 18 months after the transplant and occurs in approximately 30 percent of HLA matched sibling transplants.

Patients who get acute GvHD have a 50 percent chance of developing chronic GvHD. Both types often affect the:

  • Eyes, causing conjunctivitis, dryness and irritation, itching
  • Skin, causing rash and itching
  • Liver, causing jaundice and/or hepatitis
  • Stomach and intestinal tract, resulting in loss of appetite, cramping pain, diarrhea and vomiting

Sometimes other organs of the body, including the lungs and kidneys, also are affected. A biopsy of the affected organ is often needed to confirm the diagnosis.

GvHD can be very mild or extremely severe. There is a 10 percent to 20 percent chance of dying from GvHD. When GvHD occurs in recipients of HLA-matched sibling transplants it is usually less severe and more responsive to treatment than when it occurs following a mismatched or unrelated donor transplant.

Prevention and Treatment

There are several medications that are used to help reduce the occurrence and severity of GvHD as well as to treat it when it does occur. Two drugs that are used frequently to help minimize the reaction are methotrexate and cyclosporin A. These drugs may be given singly or in combination depending upon the type of transplant and the disease. Like all drugs, these medications may have side effects including kidney and liver injury.

Drugs which may be used to treat a reaction once it occurs include steroids, such as prednisone or methylprednisilone, cyclosporin A and anti-thymocyte globulin (ATG). In addition, there are several experimental drugs that may be offered if these standard therapies are ineffective.

In a mismatched bone marrow stem cell transplant, stem cell enrichment and T cell depletion eliminate the majority of those T lymphocytes responsible for GvHD, reducing the risk of a serious reaction to an acceptable level. Depending on the type of depletion that is done and the patient's disease, methotrexate and cyclosporin A may not be needed.