Graft-versus-leukaemia reactivity induced by alloimmunisation without augmentation of graft-versus-host reactivity

Abstract

Supralethal doses of chemoradiotherapy followed by allogeneic bone marrow transplantation are being used to treat patients with acute leukaemia refractory to conventional chemotherapy regimens1–5. Despite this approach, leukaemia has recurred in about one-third of the patients1–5. One strategy to solve this problem would be to transplant marrow with antileukaemic reactivity to obtain a graft-versus-leukaemia (GvL) effect against residual leukaemia cells6. Many workers have demonstrated antileukaemic effects following transplantation of immunocompetent cells from allogeneic donors in animal models, but graft-versus-host (GvH) disease proved to be a complication6–8. Recently, Weiden et al.9 presented evidence of a GvL effect in human recipients of marrow grafts from HLA compatible allogeneic donors. Unfortunately, this antileukaemic effect was associated with moderate, severe or lethal GvH disease, and the lower probability of recurrent leukaemia was offset by a higher probability of GvH-related mortality9. We report here the results that suggest a clinically feasible method of obtaining desired GvL effects while avoiding undesired GvH reactions. Alloimmunisation of CBA (H–2k) mice was found to induce a population of cells which, when transplanted into leukaemic AKR (H–2k) mice, led to the destruction of disseminated leukaemia (AKR-L) cells. Furthermore, the transplanted cells caused no augmentation in the mild GvH disease observed when cells from unimmunised CBA donors were administered to lethally irradiated non-leukaemic AKR hosts.