IMMUNOMODULATORY EFFECTS OF DONOR LYMPHOCYTE INFUSIONS FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION

Recently, donor lymphocyte infusions have been successfully used to tr eat patients with CML who have relapsed following allogeneic bone marr ow transplantation (BMT). Responses can be achieved in more than 60-70 % of patients with stable phase CML without the need for the additiona l high dose cytotoxic chemotherapy that would accompany a second trans plant procedure. The clinical and molecular remissions induced by this approach are a clear demonstration of graft-versus-leukemia (GVL) act ivity. Although undoubtedly donor lymphocyte infusions are safer than a second BMT, they are associated with toxicities stemming from graft- versus-host disease (GVHD) and pancytopenia. In this review, the immun omodulatory mechanisms underlying the GVL activity of donor allogeneic lymphocytes infusions are presented. Unresolved issues regarding lymp hocyte administration are discussed as well as potential ways to limit complications due to GVHD and pancytopenia. New potential application s of this immunotherapeutic approach for treatment of infectious disea se and non-hematologic malignancies will be presented. (C) 1995 Wiley- Liss, Inc.