Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many malignant and nonmalignant hematological diseases. The curative effect of allo-HSCT results from both the chemotherapy/radiation in the conditioning regimen and the donor T-mediated graft-versus-host (GVH) response against the malignancy known as a graft-versus-leukemia (GVL) effect. In most cases, the GVH response is not limited against the malignant cells but is also mediated against host epithelial cells, causing graft-versus-host disease (GVHD).

The safety and effectiveness of allogeneic transplants has increased substantially over the last several years. Despite this progress, GVHD and relapse remain the biggest hurdles for a more widespread and effective use of this potent therapy. Experimental data from recent years have provided deeper and better insights into the process of GVH responses. Emerging data have refined our understanding of the role of antigen-presenting cells (APC) in GVHD. Novel molecular targets have been identified in donor T cell subsets and host nonhematopoietic cells that can potentially be exploited for mitigating GVHD and to better harness GVL.