POSSIBLE INDUCTION OF GRAFT-VERSUS-LEUKEMIA EFFECT AGAINST A LEUKEMIA REFRACTORY TO ANTILEUKEMIA RESPONSE IN ORDINARY MHC-COMPATIBLE, ALLOGENEIC BONE MARROW TRANSPLANTATION1

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Abstract

We previously indicated that intensity of the graft-versus-leukemia(GVL) effect varied among different leukemias in MHC-compatible, allogeneic bone marrow transplantation (BMT). Cellular factors responsible for differences in intensity of the GVL effect were examined by using two types of leukemias, i.e., a resistant leukemia (LE750) and a sensitive leukemia (8313) to induction of the GVL effect in MHC-compatible, allogeneic BMT of leukemia-bearing host. Resistance of LE750 leukemic cells to induction of the GVL effect could not be attributed to either less sensitivity to lysis by minor H antigen-specific, cytotoxic T cells or to an immunosuppressive activity of LE750 leukemic cells in leukemia-bearing host, when compared with the case of the sensitive leukemia (8313). To investigate the significance of the dose effect of effector cells for induction of the GVL effect, we used CD8+ T cells of AKR donor mice, which were shown to preferentially induce the GVL effect with hardly any lethal graft-versus host disease against C3H recipient mice, enabling us to increase the number of CD8+ T cells used in the allogeneic donor inoculum. The results suggested that the outcome of the antileukemic response in allogeneic BMT of leukemic recipients may be determined, at least in part, by the balance between the size of leukemic cells surviving and repopulating in the recipients after BMT and the number of antileukemic effector cells. The results furthermore indicated that when donors with T-cell subsets that preferentially induce an antileukemic response with reduced graft-versus-host disease are available, a more effective antileukemic response is inducible even against advanced leukemias.

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