MEGADOSE OF T-CELL-DEPLETED BONE-MARROW OVERCOMES MHC BARRIERS IN SUBLETHALLY IRRADIATED MICE

Graft-versus-host disease (GVHD) is uniformly lethal in recipients of HLA-mismatched marrow. In patients with severe combined immunodeficien cy disease, this major obstacle can be overcome by rigorous T-cell dep letion before transplantation. In leukaemia patients, however, the ben efit of preventing GVHD is offset by graft rejection or graft failure, Very recently, this problem was overcome by supplementing T cell-depl eted bone marrow transplants with megadoses of peripheral blood stem c ells collected by leukapheresis after mobilization of the donor stem c ells with granulocyte colony-stimulating factor (G-CSF). In the presen t study, we further demonstrate in a mouse model (C57BL/6-->C3H/HeJ) t hat escalation of bone marrow doses by four- to fivefold leads to full donor-type chimerism in sublethally irradiated (6.5 Gy) recipients. T hus, the new source of G-CSF mobilized human haematopoietic stem cells may enable extending the use of mismatched bone marrow transplants to patients with non-malignant diseases for whom supralethal conditionin g is not a prerequisite.