Graft versus Host Disease

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The page below is a sample from the LabCE course Hematopoietic Stem Cell Transplantation. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Graft versus Host Disease

Graft versus Host Disease (GVHD) is the most common serious complication that can occur after an allogeneic HSC transplant. GVHD occurs as a result of recognition of tissue antigens in the recipient from immunologically active T cells of the donor transplant. There are two types of GVHD, acute and chronic. Together they account for significant morbidity and mortality in transplant recipients.
Acute GVHD has a rapid onset, usually within 100 days of transplant. The most commonly affected sites are skin, hepatic, gastrointestinal tract, and lung. Patients may present with a rash, elevated liver function tests (eg, alanine transaminase, alkaline phosphatase, albumin, etc.) and diarrhea. If the lungs are affected, the patient may have an infection or pulmonary embolism. Dyspnea is a frequent clinical presentation in these patients. Treatment to reduce these symptoms includes steroids and antithymocyte globulin (ATG). New antibody therapies are in clinical trials and may benefit patients who cannot tolerate steroid therapy. An interesting new therapy is extracorporeal photochemotherapy which utilizes 8-methoxypsoralen and exposes peripheral blood cells to UV-A light extracorporeally.
Chronic GVHD is a frequent cause of mortality and morbidity of patients who survive more than 100 days after transplantation. The syndrome of chronic GVHD is similar to that seen in patients with autoimmune diseases like systemic lupus erythematosus and Sjogren’s disease. The most commonly affected systems are skin, eyes, mouth, and liver. The development of chronic GVHD is more complex than acute GVHD but risk factors that have been identified include prolonged immunosuppressive therapy, increased age of the donor or patient, HLA disparity, gender differences between the donor and recipient, and the use of peripheral blood stem cells instead of bone marrow. Peripheral stem cells may have higher numbers of T-cells than bone marrow, which may account for the slight increase in GVHD risk.
Immunosuppression
There are three types of immunosuppressive drugs that can inhibit graft rejection in a patient. Steroids such as prednisone, suppress inflammation and immunologic response by inhibiting macrophage activity and reducing lymphocyte production. Cytotoxic drugs such as methotrexate and azathioprine alter DNA function in lymphocytes and decrease their production. Cyclosporine inhibits production of IL-2 cytokines by T lymphocytes and impairs the function of CD4 helper T cells.
Antilymphocyte antibodies, such as antithymocyte globulin (ATG) and anti-CD3, will impair cell-mediated immune responses by decreasing the numbers of T lymphocytes. These antibodies are also used to treat GVHD.