EFFECTIVE GRAFT-VERSUS-LEUKEMIA EFFECTS INDEPENDENT OF GRAFT-VERSUS-HOST DISEASE AFTER T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION IN A MURINE MODEL OF B-CELL LEUKEMIA LYMPHOMA - ROLE OF CELL THERAPY AND RECOMBINANT IL-2/

After allogeneic bone marrow transplantation (BMT) for leukemia, benef icial graft-vs-leukemia (CVL) effects are usually accompanied by poten tially serious graft-vs-host disease (GVHD). Because T cell depletion is the only effective way to prevent GVHD it seems important to unders tand whether effective GVL can develop after BMT with T cell depletion in GVHD-free recipients. Well-established C57BL/6-->BALB/c chimeras t hat were free of GVHD, reconstituted with T cell-depleted allogeneic b one marrow cells, and inoculated 3 mo after BMT with a high inoculatio n of murine B cell leukemia (BCL1) showed no evidence of disease, wher eas all control mice developed leukemia and died within 58 days. Resul ts from adoptive transfer experiments in secondary naive BALB/c recipi ents indicated that all BCL1 cells were eliminated in the chimeras wit hin 14 days. Hence, complete resistance to BCL1 developed in the chime ras despite complete tolerance to host alloantigens. The GVL effects o bserved in tolerant chimeras were further amplified by administration of immunocompetent allogeneic C57BL/6 spleen cells, low dose rIL-2, or both for 5 days. Our data suggest that GVL effects can develop even a fter T cell depletion in the absence of clinically overt GVHD and that GVL can be further amplified by rlL-2, either with or without use of additional immunocompetent donor T cells. Our data may provide the bas is for new approaches to induce effective GVL after allogeneic BMT wit h cell therapy and rlL-2 at the stage of minimal residual disease, whi le avoiding early GVHD induced by the BMT procedure.