Autologous graft-versus-host disease

Bone marrow transplantation (BMT) is effective therapy for patients with high-risk hematologic malignancies, and is probably the treatment of choice for patients with these diseases at relapse. Graft-versus-host disease (GVHD) develops in about 50-70% of patients undergoing allogeneic BMT and is the major cause of toxicity in these patients. Attempts to prevent GVHD by T-lymphocyte depletion of allogeneic marrow grafts have led to increased relapse rates following allogeneic BMT. Therefore, control of GVHD has not significantly improved survival after allogeneic BMT, as the decreased mortality resulting from GVHD is offset by increased relapse rates. The damaged thymus gives rise to the effector cells of syngeneic GVHD. CsA appears to augment the development of autoreactive lymphocytes by blocking mechanisms that delete autoreactive T cells in the thymus. CsA-induced autologous GVHD appears to generate immunologic antitumor activity that is similar in magnitude to that seen with allogeneic GVHD.