Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease. Bone Marrow Transplant 1993 Apr;11(4):329-36
Date
04/01/1993Pubmed ID
8485480Scopus ID
2-s2.0-0027537527 (requires institutional sign-in at Scopus site) 135 CitationsAbstract
When allogeneic BMT is used for the treatment of leukemia, depletion of T cells from the donor BM to avoid GVHD may be accompanied by persistence of host cells and post-transplant relapse. In this report, a murine model of MHC-compatible BMT was used to show that delayed infusion of immunocompetent donor cells early after T cell-deficient BMT eliminated residual host cells and provided an antileukemic effect without causing lethal GVHD. AKR (H-2k) recipient mice were pre-conditioned with 9 Gy total body irradiation (LD50) and transplanted with 10(7) BM cells from MHC-matched B10.BR donors. These mice did not develop GVHD and became stable, long-term mixed (donor-host) T cell chimeras. In this model, mixed or incomplete donor T cell chimerism was associated with decreased GVL reactivity. AKR hosts that were transplanted with B10.BR bone marrow admixed with 3 x 10(7) B10.BR spleen cells (as a source of T cells) became complete donor T cell chimeras, but they developed severe and lethal GVHD. However, when the infusion of donor spleen cells was delayed until 21 days after BMT, few mice exhibited any clinical signs of GVHD, and > 95% of the mice became long-term survivors. The infused spleen cells eliminated residual host T cells by 21 days after infusion, and most chimeras were able to resist a supralethal challenge with AKR leukemia/lymphoma cells. Thus, post-transplant adoptive immunotherapy with normal mononuclear cells from the marrow donor may be an effective way to eliminate residual disease or treat leukemia relapse after BMT without causing significant GVHD.
Author List
Johnson BD, Drobyski WR, Truitt RLAuthors
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinBryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Robert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AKR murine leukemia virusAnimals
Bone Marrow Transplantation
Female
Graft vs Host Disease
Graft vs Host Reaction
Immunotherapy, Adoptive
Leukemia, Experimental
Lymphocyte Depletion
Mice
Mice, Inbred AKR
Polymerase Chain Reaction
Postoperative Period
Radiation Chimera
Spleen
T-Lymphocytes
Time Factors
Transplantation, Homologous
