A Phase II Study of the Impact of Two Different Schedules of Thymoglobulin on the Incidence of Extensive Chronic Graft Verus Host Disease (GVHD) in Patients Undergoing Unrelated Donor or Mismatched Related Donor Stem Cell Transplantation

This study is for patients with a condition in which it has been recommended that an unrelated or (less commonly) a mismatched related donor stem cell transplant be performed. One of the major side-effects of receiving a peripheral blood stem cell transplant from an unrelated or mismatched related donor is graft vs host disease (GVHD), particularly extensive chronic GVHD which can occur in up to 80% of patients. Some forms of chronic GVHD, particularly of the skin, lung and liver, can be debilitating, respond poorly to therapy and result in significant impairment of quality of life and can lead to death. The type of donor cells which are responsible for GVHD are called T cells. The number of T cells can be substantially reduced by giving the patient a drug, for three days prior to the transplant, called thymoglobulin. This drug is derived from rabbits and is an antibody which inactivates or “depletes” many of the T cells as they are infused. Evidence from various studies suggests that T cell depletion of this type can substantially reduce the risk of GVHD after a transplant, with major improvements in the quality of life in surviving patients. There are, however, potential disadvantages from T cell depletion. The same T cells which cause GVHD may also be important for engraftment (the ability of the donor stem cells to grow successfully in the recipients bone marrow and restore blood counts), immunity against viral infections (particularly in the first 3-4 months post-transplant) and a graft vs leukaemia/lymphoma effect which is when the immune system of the donor attacks any residual tumour which has survived the chemotherapy and radiotherapy.