ERADICATION OF RESIDUAL DISEASE BY ADMINISTRATION OF LEUKEMIA-SPECIFIC T-CELLS AFTER EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

It is now well established that allogeneic lymphocytes can mediate a p otent graft-vs.-leukemia (GVL) reaction when administered to bone marr ow transplant (BMT) recipients. The benefit of allogeneic lymphocyte t ransfusion is limited because many patients develop graft-vs.-host dis ease (GVHD) with prolonged pancytopenia, which sometimes proves fatal. The object of the present study was to determine the antileukemic pot ential and GVHD risk of in vivo-generated tumor-specific allogeneic T cells given shortly after BMT. BALB/C (H-2d) mice were inoculated with different cell doses (10(5) and 5 x 10(5)) of the A20 leukemia (BALB/ C origin) 2 days prior to lethal total-body irradiation (TBI) and tran splantation of allogeneic, major histocompatibility complex (MHC)-matc hed DBA marrow grafts (H-2(d), minor difference to BALB/C). Donors of BM grafts and T cells were allogeneic, MHC-matched mice (DBA, H-2(d) m inor difference to BALB/C). Donor-type T cells were generated from mic e immunized with irradiated A20 leukemia cells or nonmalignant BALB/C splenocytes and restimulated in vitro. Whereas no significant immunoth erapeutic effect was seen in mice with high tumor burden (5 x 10(5)), allogeneic BMT in mice inoculated with 1 x 10(5) A20 cells resulted in a modest antileukemic effect. This survival rate remained unchanged w hen 10(6) T cells obtained from donors immunized with nonmalignant BAL B/C derived cells were given posttransplantation. In contrast, a singl e injection of 10(6) T cells from leukemia-immunized donors led to pot ent GVL effects without mediating clinically overt GVHD. Our data prov ide evidence for the hypothesis that minimal residual disease can be e radicated without inducing GVHD by administering small amounts of spec ific allogeneic cytotoxic T cells after BMT.