Impact on early outcomes and immune reconstitution of high-dose post-transplant cyclophosphamide vs anti-thymocyte globulin after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation

// Christelle Retière 1 , 2, 8 , Catherine Willem 1, 2, 8 , Thierry Guillaume 2, 3, 8 , Henri Vié 1, 2, 8 , Laetitia Gautreau-Rolland 2, 8 , Emmanuel Scotet 2, 8 , Xavier Saulquin 2, 8 , Katia Gagne 1, 2, 4, 8 , Marie C. Béné 5, 8 , Berthe-Marie Imbert 6, 7, 8 , Beatrice Clemenceau 2, 8 , Pierre Peterlin 3 , Alice Garnier 3 and Patrice Chevallier 2, 3, 8 1 Etablissement Français du Sang, Nantes, France 2 CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France 3 Hematology Department, CHU, Nantes, France 4 LabEx Transplantex, Université de Strasbourg, France 5 Hematology/Biology Department, CHU, Nantes, France 6 INSERM, Centre de Recherche en Transplantation et Immunologie, UMR1064, Université de Nantes, Nantes, France 7 Service de Virologie, CHU Nantes, Nantes, France 8 LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, F-44000, France Correspondence to: Christelle Retière, email: christelle.retiere@efs.sante.fr Keywords: allogeneic bone marrow transplantation; post-transplant cyclophosphamide; immune reconstitution; immunology Received: May 31, 2017      Accepted: November 01, 2017      Published: January 27, 2018 ABSTRACT We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen. The γ/δ T-cells, α/β T-cells (CD8 + and CD4 + ), NK T-cells, NK cells, B-cells, Tregs and monocytes were analyzed by flow cytometry from a total of 583 samples. In the PTCY group significant delayed platelets recovery, higher CD3+ donor chimerism, higher HHV-6 and lower EBV reactivations were observed. Early survival advantage for CD4+ T-cells, Tregs and α/β T-cells was documented in the PTCY group while it was the case for α/β T-cells, NK cells and monocytes in the ATG group. Higher counts of NK and monocytes were observed at days +30 and/or day+60 in the ATG group. Both results were retained even in the case of mismatched donors. However, higher percentages of CD4+ T-cells, α/β T-cells and Tregs were observed with haplo-identical donors in the PTCY group. Finally, clofarabine was responsible for early survival advantage of NK T-cells in the PTCY group while it abrogated the early survival advantage of γ/δ T-cells in the ATG group. In conclusion, there are marked differences in the immunological effects of ATG vs PTCY as GVHD prophylaxis for RIC PBSC allo-SCT.