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Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution

Dhon Roméo Makanga, Thierry Guillaume, Catherine Willem, Nolwenn Legrand, Katia Gagne, Anne Cesbron, Ketevan Gendzekhadze, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marie C. Béné, Patrice Chevallier and Christelle Retière
J Immunol September 1, 2020, 205 (5) 1441-1448; DOI: https://doi.org/10.4049/jimmunol.2000578
Dhon Roméo Makanga
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
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Thierry Guillaume
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
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  • ORCID record for Thierry Guillaume
Catherine Willem
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
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Nolwenn Legrand
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
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Katia Gagne
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
§LabEx Transplantex, Université de Strasbourg, 67000 Strasbourg, France;
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Anne Cesbron
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
§LabEx Transplantex, Université de Strasbourg, 67000 Strasbourg, France;
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Ketevan Gendzekhadze
¶Histocompatibility Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010;
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Pierre Peterlin
‖Hematology Clinic, Centre Hopitalier-Universitaire, 44000 Nantes, France; and
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Alice Garnier
‖Hematology Clinic, Centre Hopitalier-Universitaire, 44000 Nantes, France; and
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Amandine Le Bourgeois
‖Hematology Clinic, Centre Hopitalier-Universitaire, 44000 Nantes, France; and
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Marie C. Béné
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
#Hematology Biology, Centre Hopitalier-Universitaire, 44000 Nantes, France
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Patrice Chevallier
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
‖Hematology Clinic, Centre Hopitalier-Universitaire, 44000 Nantes, France; and
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Christelle Retière
*Etablissement Français du Sang, Centre-Pays de la Loire, 44011 Nantes, France;
†Université de Nantes, CNRS, INSERM, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, 44000 Nantes, France;
‡Laboratoire d’Excellence Immunotherapy Graft Oncology, 44000 Nantes, France;
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Key Points

  • PTCY + ATG versus PTCY limits the occurrence of grade 2–4 acute GVHD after RIC PBSC h-HSCT.

  • Quicker reconstitution of some NK cell subtypes may help to avoid relapse.

Abstract

A higher incidence of graft-versus-host disease (GVHD) has been observed after haploidentical hematopoietic stem cell transplantation (h-HSCT) with posttransplant cyclophosphamide (PTCY) using peripheral blood stem cells (PBSC) as a source of graft. Moreover, combining PTCY with antithymocyte globulin (ATG) may help to reduce GVHD incidence. In this study, early immune reconstitution, especially of T and NK cell compartments, was compared after both types of transplant (PTCY versus PTCY + ATG) investigate their influence on patient outcomes. This retrospective study included 58 adults who received a reduced intensity conditioning to PBSC h-HSCT with cyclosporine and mycophenolate mofetyl + PTCY (n = 32) or PTCY + ATG (n = 26) as GVHD prophylaxis. Both groups shared similar characteristics except for the median number of CD3+ T cells infused, significantly higher for PTCY + ATG patients. Blood samples from all patients were collected three times a week from day 0 until day 30 then at day 60 and day 90/100 to evaluate T and NK cells reconstitution by flow cytometry. The results show that PTCY + ATG versus PTCY alone significantly limits the occurrence of acute grade 2–4 GVHD after reduced intensity conditioning PBSC h-HSCT, perhaps because of the combined effect of T and NK cell reconstitution. Indeed, although a slower T cell reconstitution with PTCY + ATG may limit GVHD occurrence, the quicker reconstitution of some NK cell subtypes may help with avoiding relapse. Larger prospective studies are needed to better determine which NK cell subsets may influence the incidence of relapse after h-HSCT and optimize donor selection.

Footnotes

  • ↵1 P.C. and C.R. have equally contributed to this work.

  • This work was supported by the Etablissement Français du Sang/Centre Pays de la Loire and by grants from the International Research Group on Unrelated Hematopoietic Stem Cell Transplantation, la Ligue contre le Cancer (Comité de Loire-Atlantique, Comité de la Vienne, Comité de la Vendée, Comité du Morbihan et le Comité des Deux Sèvres), le Département Hospitalo-Universitaire Oncogreffe, Leucémie Espoir Atlantique Famille, and Agence de Biomédecine. D.R.M. is a Ph.D. student supported by Industrial Agreement for Training through Research Grant 2017/0850.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    ALL
    acute lymphoblastic leukemia
    AML
    acute myeloid leukemia
    ATG
    antithymocyte globulin
    BM
    bone marrow
    D
    donor
    DFS
    disease-free survival
    GRFS
    GVHD-free/relapse-free survival
    GVHD
    graft-versus-host disease
    GvL
    graft-versus-leukemia
    h-HSCT
    haploidentical hematopoietic stem cell transplantation
    HSCT
    hematopoietic stem cell transplantation
    inc.
    incompatibility
    KIR
    killer Ig-like receptor
    NRM
    nonrelapse mortality
    OS
    overall survival
    PBSC
    peripheral blood stem cell
    PTCY
    posttransplant cyclophosphamide
    R
    recipient
    RIC
    reduced intensity conditioning.

  • Received May 19, 2020.
  • Accepted July 4, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 205 (5)
The Journal of Immunology
Vol. 205, Issue 5
1 Sep 2020
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Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution
Dhon Roméo Makanga, Thierry Guillaume, Catherine Willem, Nolwenn Legrand, Katia Gagne, Anne Cesbron, Ketevan Gendzekhadze, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marie C. Béné, Patrice Chevallier, Christelle Retière
The Journal of Immunology September 1, 2020, 205 (5) 1441-1448; DOI: 10.4049/jimmunol.2000578

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Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution
Dhon Roméo Makanga, Thierry Guillaume, Catherine Willem, Nolwenn Legrand, Katia Gagne, Anne Cesbron, Ketevan Gendzekhadze, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marie C. Béné, Patrice Chevallier, Christelle Retière
The Journal of Immunology September 1, 2020, 205 (5) 1441-1448; DOI: 10.4049/jimmunol.2000578
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