• Muriel Hannon, Yves Beguin, Grégory Ehx, Sophie Servais, Laurence Seidel, Carlos Graux, Johan Maertens, Tessa Kerre, Coline Daulne, Muriel de Bock, Marianne Fillet, Aurélie Ory, Evelyne Willems, André Gothot, Stéphanie Humblet-Baron, and Frédéric Baron.
• Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-I3, University of Liège, Liège, Belgium. m.hannon@chu.ulg.ac.be.
• Clin Cancer Res. 2015 Jul 15; 21 (14): 3131-9.

PurposeA 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 DesignWe 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).ResultsIn 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 naïve 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/naïve CD4(+) T-cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation.ConclusionsImmune recovery differs substantially between these two conditioning regimens, possibly explaining the different clinical outcomes observed (NCT00603954).©2015 American Association for Cancer Research.

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