Graft Vs. Host Disease (GVHD)

Graft vs. host disease (GVHD) is a complication that may occur during the post-transplant period in children who receive marrow stem cells from other individuals including HLA matched siblings,  parents and unrelated donors. GVHD reactions can occur when cells of the donor’s immune system (T lymphocytes) are infused (via a blood or platelet transfusion or a bone marrow transplant) into the recipient (i.e., the host) who has received conditioning therapy. Blood and platelets are irradiated to prevent GVHD, but the donor graft cannot be treated this way since irradiation would also kill the normal bone marrow stem cells.

Types and manifestations of GVHD

GVHD can take two forms, acute and chronic. Acute GVHD usually develops within 3 months of the transplant and occurs in 20-25% of HLA matched sibling transplants in children and 30-35% in adults. Chronic GVHD usually develops 3-18 months post-BMT and occurs in approximately 30% of HLA matched sibling transplants. Patients who get acute GVHD have a 50% chance of developing chronic GVHD. Both types often affect the eyes (conjunctivitis, dryness and irritation, itching), skin (rash, itching), liver (jaundice and/or hepatitis) and stomach and intestinal tract (loss of appetite, crampy pain, diarrhea and vomiting) and sometimes other organs of the body including the lungs and kidneys. A biopsy of the affected organ is often needed to confirm the diagnosis. GVHD can be very mild or extremely severe. There is a 10-20% 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 of GVHD

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 (prednisone or methylprednisilone), cyclosporin A (if not already being administered), and anti-thymocyte globulin (ATG). In addition, there are several experimental drugs which 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, and reduce 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.