DELAYED INFUSION OF NORMAL DONOR CELLS AFTER MHC-MATCHED BONE-MARROW TRANSPLANTATION PROVIDES AN ANTILEUKEMIA REACTION WITHOUT GRAFT-VERSUS-HOST DISEASE

When allogeneic BMT is used for the treatment of leukemia, depletion o f T cells from the donor BM to avoid GVHD may be accompanied by persis tence of host cells and post-transplant relapse. In this report, a mur ine model of MHC-compatible BMT was used to show that delayed infusion of immunocompetent donor cells early after T cell-deficient BMT elimi nated residual host cells and provided an antileukemic effect without causing lethal GVHD. AKR (H-2k) recipient mice were pre-conditioned wi th 9 Gy total body irradiation (LD50) and transplanted with 10(7) BM c ells from MHC-matched B10.BR donors. These mice did not develop GVHD a nd became stable, long-term mixed (donor-host) T cell chimeras. In thi s model, mixed or incomplete donor T cell chimerism was associated wit h decreased GVL reactivity. AKR hosts that were transplanted with B10. BR bone marrow admixed with 3 x 10(7) B10.BR spleen cells (as a source of T cells) became complete donor T cell chimeras, but they developed severe and lethal GVHD. However, when the infusion of donor spleen ce lls was delayed until 21 days after BMT, few mice exhibited any clinic al signs of GVHD, and >95% of the mice became long-term survivors. The infused spleen cells eliminated residual host T cells by 21 days afte r infusion, and most chimeras were able to resist a supralethal challe nge with AKR leukemia/lymphoma cells. Thus, post-transplant adoptive i mmunotherapy with normal mononuclear cells from the marrow donor may b e an effective way to eliminate residual disease or treat leukemia rel apse after BMT without causing significant GVHD.