Adoptive immunotherapy with donor lymphocyte transfusions

Adoptive immunotherapy denotes the transfer of immunocompetent cells for the treatment of leukemia, cancer, or viral disease. It has regained much interest through the success of treating recurrent leukemia after allogeneic bone marrow transplantation with the transfusion of donor lymphocytes. Chimerism and transplantation tolerance toward the donor offer the possibility of adoptive immunotherapy using donor lymphocytes. In animal studies, donor lymphocytes could be transfused into the chimeric animal, if the transfusion was delayed after marrow transplantation. Transfused lymphocytes exhibit a graft-versus-leukemia effect and increase chimerism. Immunity could be transferred and immune reactivity toward new antigens improved. In human patients transfusion of donor lymphocytes was studied in leukemia recurring after marrow transplantation. It was very effective in the treatment of chronic myelogenous leukemia recurring after marrow transplantation. It was also effective in some patients with acute myeloid leukemia, myelodysplastic syndrome and myeloma; in acute lymphoblastic leukemia and lymphoma responses were rare. Responses in solid tumors as breast cancer have been described. Major complications are graft-versus-host disease and myelosuppression. Myelosuppression could be compensated by the transfusion of marrow. Graft-versus-host disease can be modified by the depletion of CD8-positive T cells from the lymphocyte concentrate or by transfusing very low numbers of cells and increasing doses in a stepwise fashion. The role of concomitant treatment with cytokines and activation of T cells by dendritic cells and vaccination remains to be defined.