Key Points Cytomegalovirus after bone marrow transplantation remains associated with lower survival but not prevention of leukemia relapse.

Chronic graft-versus-host disease (cGVHD) is the leading cause of late treatmentrelated deaths among recipients of allogeneic bone marrow and blood transplants. However, cGVHD is also associated with fewer relapses. We sought to determine whether severity of cGVHD predicts the magnitude of these effects. One impediment to such an analysis is the current limited/extensive grading system for cGVHD because this classification was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of multiorgan involvement. We, therefore, first developed a grading system predictive for survival by using data from 1827 HLAmatched sibling allotransplant recipients reported to the International Bone Marrow Transplant Registry (IBMTR). We found Karnofsky performance score, diarrhea, weight loss, and cutaneous and oral involvement to be independent prognostic variables, from which we generated a grading scheme. We tested this scheme, the limited/extensive classification sys-

Regulatory T cells (T reg s) that constitutively express FOXP3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in humans. To determine whether regulatory T cells in allogeneic stem cell transplants (SCTs) ameliorate GVHD after transplantation, we quantitated the coexpression of FOXP3 on CD4 ؉ T cells in 32 donor SCTs infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4 ؉ FOXP3 ؉ Tcell count in the donor was associated with a reduced risk of GVHD. We monitored T reg s during immune reconstitution in 21 patients with leukemia undergoing a T-cell-depleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4 ؉ FOXP3 ؉ T-cell compartment. A low CD4 ؉ FOXP3 ؉ Tcell count early after SCT (day 30) was associated with an increased risk of GVHD, and the ratio of CD4 ؉ FOXP3 ؉ T cells to CD4 ؉ CD25 ؉ FOXP3 ؊ T cells was significantly reduced in patients with GVHD, suggesting diminished control of effector T cells. Our findings suggest that graft T reg content may predict for risk of GVHD after SCT. Determining the T reg levels in the donor and manipulating T reg s early after transplantation may provide a new approach to