Improving outcome of allogeneic stem cell transplantation by immunomodulation of the early post-transplant environment

There has been great progress in understanding the alloresponse and the process of immune recovery after stem cell transplantation. Here, we highlight ways in which transplant outcome is determined by unique immunological features of the early post-transplant period that modulate the growth and function of the grafted donor T cells and stem cells. Better understanding of these early events and more detailed knowledge of the phenotype and function of transplanted donor cells facilitate strategies to optimize immune recovery, prevent graft-versus-host disease (GVHD) and boost immunity to viruses and leukemia. Approaches that optimize CD34 cell dose, techniques to remove GVHD-reacting T cells by T cell subset selection, suicide gene insertion or selective allodepletion, and the adoptive transfer of antigen-specific T cells have reached the stage of clinical trials. Furthermore, murine transplant experiments indicate ways to prevent GVHD while preserving immune function by depletion of naïve cells, T cytotoxic 1 and T helper 1 cells, or by enrichment of regulatory T cells. Many of these approaches appear feasible in clinical transplantation and have yielded promising initial results, but proof that the goal of controlled selective immune reconstitution can be achieved is still awaited.