Induction of Mixed vs Full Chimerism to Potentiate GVL Effects After Bone-Marrow Transplantation

Graft-vs-host (GVH) alloresponses mediated by delayed donor lymphocyte infusions (DLI) can occur in the absence of GVHD (graft-vs-host disease). These GVH responses are confined to the lymphohematopoietic system and mediate graft-vs-leukemia (GVL) reactions without causing GVHD. Although interaction of donor T-cells with host-derived antigen-presenting cells (APC) is central to the development of GVHD, we were able to show that this T-cell/APC interaction is also critical for the induction of GVL, which can occur in the absence of GVHD if donor T-cell administration is delayed to a time point after bone-marrow transplant (BMT) when conditioning-induced inflammation has subsided. Induction of mixed hematopoietic chimerism using the method described below allows analysis of these interactions between host APC and donor T-cells.