 Allogeneic hematopoietic stem cell transplantation HSCT is potentially curative for refractory hematologic malignancies, but its application has been limited historically by morbidity and mortality from conventional transplant preparative regimens and graft-versus-host disease GVHD. Donor T cells mediate GVHD and also help to eradicate malignancies through an immune-dependent graft-versus-tumor effect. Efforts to decrease preparative regimen toxicity have led to reduced-intensity or nonmyeloablative regimens, facilitating the study of allogeneic HSCT in a broader population. As a promising strategy for reducing GVHD, donor Th2 cells were shown to abrogate Th1-mediated GVHD without impairing engraftment in murine models of allogeneic HSCT. These findings led to a phase III clinical study of donor Th2 cells for the prevention of GVHD during reduced-intensity allogeneic HSCT CC 99-C-0143; preliminary results suggest that a randomized trial will be necessary to evaluate donor Th2 cells further. 