Oncotarget

Research Papers: Immunology:

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 _, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C. Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier and Patrice Chevallier

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Oncotarget. 2018; 9:11451-11464. https://doi.org/10.18632/oncotarget.24328

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Abstract

Christelle Retière1,2,8, Catherine Willem1,2,8, Thierry Guillaume2,3,8, Henri Vié1,2,8, Laetitia Gautreau-Rolland2,8, Emmanuel Scotet2,8, Xavier Saulquin2,8, Katia Gagne1,2,4,8, Marie C. Béné5,8, Berthe-Marie Imbert6,7,8, Beatrice Clemenceau2,8, Pierre Peterlin3, Alice Garnier3 and Patrice Chevallier2,3,8

1Etablissement Français du Sang, Nantes, France

2CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France

3Hematology Department, CHU, Nantes, France

4LabEx Transplantex, Université de Strasbourg, France

5Hematology/Biology Department, CHU, Nantes, France

6INSERM, Centre de Recherche en Transplantation et Immunologie, UMR1064, Université de Nantes, Nantes, France

7Service de Virologie, CHU Nantes, Nantes, France

8LabEx IGO “Immunotherapy, Graft, Oncology”, Nantes, F-44000, France

Correspondence to:

Christelle Retière, email: [email protected]

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.


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