Balance between GVT and GVHD after T cell–replete or T cell–depleted transplantation. (A) T cell–replete alloSCT: conditioning regimen induced tissue damage and pathogens mediate activation of recipient APC, lymphopenia-associated homeostatic proliferation, and an inflammatory cytokine milieu resulting in highly diverse and high-magnitude alloimmune T-cell responses causing simultaneous GVT and GVHD reactivity, requiring posttransplant immune suppression. (B) T-cell depletion abrogates GVT and GVHD early after transplantation, resulting in an increased risk of relapse and lack of control of pathogens. Postponed donor T-cell infusions (donor lymphocyte infusion [DLI]) are needed for GVT reactivity: the risk of GVHD is lower due to tissue repair, less inflammation, and replacement of recipient APC by donor APC.