Pathophysiology and management of graft-versus-host disease in the era of reduced-intensity conditioning.

Both indirect and direct effects contribute to changes in the clinical presentation of graft-versus-host disease (GvHD) after reduced-intensity conditioning (RIC) compared with standard intensity regimens. A delay in acute GvHD after RIC may be explained by reduced conditioning-related inflammation and by altered allostimulatory capacities of recipient antigen-presenting cells (APC). A higher frequency of chronic GvHD results from the almost exclusive use of peripheral blood stem cells, the absence of tolerance induction by current regimens for prophylactic immunosuppression and modified kinetics in the replacement of recipient APC. Established acute and chronic GvHD requires standard treatment irrespective of the type of conditioning. To improve long-term outcome in GvHD, pre-emptive strategies or more selective approaches aimed at immunomodulation rather than immunosuppression are needed.