Graft-Vs-Host Disease (GVHD)

Introduction

Graft-versus-host disease (GVHD) is often a much too frequent complication of allogeneic Bone Marrow Transplants (BMT). Bone marrow transplants are given to treat malignant and nonmalignant diseases such as leukemia, lymphoma, marrow failure also known as aplastic anemia, metabolic disorders, HIV, Inherited red cell disorders (Gratwohl, 2006). Bone marrow can be taken from umbilical cord blood, peripheral blood stem cells and from bone marrow itself from various donors. They can be obtained from either autologous which is from the recipient themselves or from an allogeneic donor which is from someone else either related or unrelated. GVHD, it is when the donor's bone marrow attacks the recipients organs and tissues, impairing
Transplants are done with increasing measures of mismatch to reduce toxicity and transplant mortality by using nonmyeloblative therapy (produces minimal cytopenia) with increased suppression around the time of transplant and post transplant to obtain a partial graft followed by DLI to accomplish complete remission. DLI is also used in patients when relapse follows transplant. Gene therapy is type of stem cell in which the deficiency is corrected and then re-transplanted similarly to auto-BMT, therefore, smaller doses of chemotherapy are needed and risks of getting GVHD are abolished. While advancements are being made in gene transfer and expression research is expanding to include diseases such as HIV, betathalassemia, sickle cell, multiple sclerosis, lupus, and juvenile rheumatoid arthritis. Further research is also being made to de-differentiate cells into induced pluripotent stem cells, which allows the ability to correct the mutation in vitro, thus stimulating the cells to differentiate into stem cells for transplantation (Gratwohl, 2006). T-cell depletion is another method being researched and currently used in trials to reduce the severity of GVHD. T-cells in the body detect foreign antigens, and T-cells when removed decrease the incidence from 50% to about 15%. However, T-cells also are necessary for a successful engraftment of the new bone marrow in the recipient (Bader, et al., 2010). It is essentially a double edged sword. T-cell depletion reduces the risk of GVHD but relapse of the disease increased. The key challenge of allo-BMT is to prevent GVHD without losing the graft versus leukemia effect (GVL); which is the ability of the donors cells to eradicate the cancer with the “donated” T-cells to react against the leukemic cells further destroying