Increased frequencies of CD4+CD25high Tregs correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.

The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4+CD25high regulatory T cells (Tregs) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4+CD25high Tregs in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of Tregs in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the Tregs purified from SCT patients exhibited a more potent suppressive activity than Tregs isolated from healthy volunteers. Patients in whom Tregs numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in Tregs might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that Tregs exert an inhibitory effect on GvL.Leukemia (2007) 21, 472–479. doi:10.1038/sj.leu.2404522; published online 18 January 2007 [ABSTRACT FROM AUTHOR]