Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been developed to induce graft-versus-tumor effects without graft-versus-host disease (GVHD). Experimental Design: We compared immune recovery in 53 patients included in a phase II randomized study comparing nonmyeloablative HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n = 28) or 8 Gy TLI plus ATG (TLI arm, n = 25). Results: In comparison with TBI patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute GVHD, a lower incidence of moderate/severe chronic GVHD (P = 0.02), a higher incidence of CMV reactivation (P < 0.001), and a higher incidence of relapse (P = 0.01). While recovery of total CD8(+) T cells was similar in the two groups, with median CD8(+) T-cell counts reaching the normal values 40 to 60 days after allo-HCT, TLI patients had lower percentages of naive CD8 T cells. Median CD4(+) T-cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Furthermore, CD4(+) T-cell counts were significantly lower in TLI than in TBI patients the first 6 months after transplantation. Interestingly, while median absolute regulatory T-cell (Treg) counts were comparable in TBI and TLI patients, Treg/naive CD4(+) T-cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation. Conclusions: Immune recovery differs substantially between these two conditioning regimens, possibly explaining the different (C) 2015 AACR.