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 immunodeficiency disease, this major obstacle can be overcome by rigorous T-cell depletion before transplantation. In leukaemia patients, however, the benefit of preventing GVHD is offset by graft rejection or graft failure. Very recently, this problem was overcome by supplementing T cell-depleted bone marrow transplants with megadoses of peripheral blood stem cells collected by leukapheresis after mobilization of the donor stem cells with granulocyte colony-stimulating factor (G-CSF). In the present study, we further demonstrate in a mouse model (C57BL/6-->C3H/Hej) that escalation of bone marrow doses by four- to fivefold leads to full donor-type chimerism in sublethally irradiated (6.5 Gy) recipients. Thus, 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 conditioning is not a prerequisite.
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006822:Hybrid Cells / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014916:Whole-Body Irradiation
D016179:Granulocyte Colony-Stimulating Factor