Adoptive immunotherapy represents a new therapeutic tool able to eradicate or to improve the course of various hematological malignancies and solid tumors. Alloreactive lymphocytes present within the hematopoietic transplant have been shown to be responsible for the occurrence of acute and chronic graft-versus-host-disease (GVHD). Retrospective analysis of survival curves after allogeneic bone marrow transplantation performed for leukemia have shown that GVHD was accompanied with lower relapse rates suggesting graft-versus leukemia (GVL) affect. T cell-depletion demonstrated the inverse balance existing between GVHD/GVL and relapse. Allogeneic bulk lymphocyte infusions were further used for successful treatment of relapse after transplantation in CML patients. However they were responsible for some cases of lethal acute GVHD and myelosuppressions in some patients. The concept of allogeneic transplantations after reduced intensity conditioning regimen (RICT) has recently emerged as a new strategy to treat cancer. This strategy exploited the immunological properties of the graft followed or not by donor lymphocyte infusions (DLI) while reducing the toxicity of the preparative regimen. Different means to perform RICT have been described, however the systematic use of DLI (bulk or escalating doses) after these transplantations remains controversial. Hereby, we report a summary of historical data that lead to the concept of adoptive immunotherapy and its applications.
John Libbey Eurotext 2003