Separating graft-versus-tumor from graft-versus-host reactions.
The full therapeutic potential of allogeneic stem cell transplantation, through its immunologically mediated graft-versus-tumor effect, in patients with hematologic malignancies is greatly compromised by the occurrence of graft-versus-host disease. Unfortunately, the use of non-selective immunosuppressive agents to reduce the incidence and severity of graft-versus-host disease is associated with severe immune compromise of the host and most likely a greater relapse risk of the underlying malignancy. Many attempts have been made to clinically separate these two effects. A critical overview of the published experience is the focus of this report. As the effector cells responsible for the two reactions are largely unknown, the limited success of the various approaches used is not surprising. A more thorough understanding of the antigenic stimuli involved in the initiation of the two reactions and of the molecular pathways through which the cytotoxic effects of T-cells are mediated is essential for abrogating graft-versus-host disease while preserving the graft-versus-tumor effect.
Fassas
A B T
AB
Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock 72205, USA. fassasathanasios@uams.edu
Morris
C
C
Badros
A
A
Van Rhee
F
F
Tricot
G
G
D000818:Animals; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006087:Graft vs Host Reaction / Q000276:immunology*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007938:Leukemia / Q000628:therapy; D008212:Lymphocyte Depletion; D033581:Stem Cell Transplantation