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

Abstract

<div>Abstract<p><b>Purpose:</b> 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).</p><p><b>Experimental Design:</b> 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, <i>n</i> = 28) or 8 Gy TLI plus ATG (TLI arm, <i>n</i> = 25).</p><p><b>Results:</b> 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 (<i>P</i> = 0.02), a higher incidence of CMV reactivation (<i>P</i> < 0.001), and a higher incidence of relapse (<i>P</i> = 0.01). While recovery of total CD8<sup>+</sup> T cells was similar in the two groups, with median CD8<sup>+</sup> T-cell counts reaching the normal values 40 to 60 days after allo-HCT, TLI patients had lower percentages of naïve CD8 T cells. Median CD4<sup>+</sup> T-cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Furthermore, CD4<sup>+</sup> 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/naïve CD4<sup>+</sup> T-cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation.</p><p><b>Conclusions:</b> Immune recovery differs substantially between these two conditioning regimens, possibly explaining the different clinical outcomes observed (NCT00603954). <i>Clin Cancer Res; 21(14); 3131–9. ©2015 AACR</i>.</p></div>