Graft manipulation and GVHD: what goes around comes around

In this issue of Blood, Meyer et al 1 report the results of a prospective randomized trial comparing Orca-T, a T-cell deconstructed and reconstructed allogeneic mobilized peripheral blood graft, with a conventional unmanipulated peripheral blood graft using tacrolimus plus methotrexate as graftversus-host disease (GVHD) prophylaxis.The Orca-T product comprised a CD34-selected T-cell-depleted graft with the additional infusion of freshly isolated donor regulatory T cells on day 0 and conventional T cells on day +2 or +3.This trial was performed in HLA-matched transplants after myeloablative conditioning; with a median follow-up of nearly a year, Orca-T achieved its primary end point, superior chronic GVHD-free survival compared with the control arm (78.0%vs 38.4%; P < .001).Notably, nonrelapse mortality (NRM) was lower in the Orca-T arm than in the control arm (3.4% vs 13.2%; P = .03);with limited follow-up, there were no significant differences in relapse rates, disease-free survival (DFS), or overall survival (OS) between the 2 arms.