Progressive microangiopathy distinguishes sensitive and refractory clinical courses of GVHD. The working hypothesis is as follows: Sensitive and refractory patients both have a T-cell attack (gray triangle) that responds to standard (sensitive) or salvage (refractory) immunosuppressive therapy. Epithelial apoptosis (thick line) is induced by T cells in sensitive patients and responds to immunosuppressive therapy after clearing the T-cell response (top panel). In contrast to sensitive patients, steroid-refractory patients have a vulnerable endothelial system that reacts to the initiating T-cell attack with progressive endothelial damage. This microangiopathy may cause organ failure and promote epithelial apoptosis, although the initiating T-cell attack was cleared (bottom panel).