Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis
IntroductionPoor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to hel...
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Frontiers Media S.A.
2023-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1106464/full |
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author | Sophie Servais Frédéric Baron Chantal Lechanteur Laurence Seidel Etienne Baudoux Alexandra Briquet Dominik Selleslag Johan Maertens Xavier Poire Wilfried Schroyens Carlos Graux Ann De Becker Pierre Zachee Aurélie Ory Julie Herman Tessa Kerre Yves Beguin |
author_facet | Sophie Servais Frédéric Baron Chantal Lechanteur Laurence Seidel Etienne Baudoux Alexandra Briquet Dominik Selleslag Johan Maertens Xavier Poire Wilfried Schroyens Carlos Graux Ann De Becker Pierre Zachee Aurélie Ory Julie Herman Tessa Kerre Yves Beguin |
author_sort | Sophie Servais |
collection | DOAJ |
description | IntroductionPoor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT.MethodsWe prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330).ResultsWithin 90 days post-MSC infusion, 53% (95% CI, 35 – 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 109/L, Hb > 80g/L and platelet count > 20 x 109/L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 109/L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 – 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention.DiscussionIn conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results. |
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spelling | doaj.art-268dc62031e34eaea9935539979eaca42023-02-01T07:56:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11064641106464Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysisSophie Servais0Frédéric Baron1Chantal Lechanteur2Laurence Seidel3Etienne Baudoux4Alexandra Briquet5Dominik Selleslag6Johan Maertens7Xavier Poire8Wilfried Schroyens9Carlos Graux10Ann De Becker11Pierre Zachee12Aurélie Ory13Julie Herman14Tessa Kerre15Yves Beguin16Department of Clinical Hematology, University Hospital Center and University of Liège, Liège, BelgiumDepartment of Clinical Hematology, University Hospital Center and University of Liège, Liège, BelgiumLaboratory of Cell and Gene Therapy, University Hospital Center and University of Liège, Liège, BelgiumDepartment of Biostatistics, SIMÉ, University Hospital Center and University of Liège, Liège, BelgiumLaboratory of Cell and Gene Therapy, University Hospital Center and University of Liège, Liège, BelgiumLaboratory of Cell and Gene Therapy, University Hospital Center and University of Liège, Liège, BelgiumDepartment of Clinical Hematology, AZ Sint-Jan Brugge-Oostende AV, Bruges, BelgiumDepartment of Clinical Hematology, University Hospital Leuven, Leuven, BelgiumDepartment of Clinical Hematology, Cliniques Universitaires Saint-Luc, Brussels, BelgiumDepartment of Clinical Hematology, Antwerp University Hospital, Edegem, BelgiumDepartment of Clinical Hematology, Université Catholique de Louvain, University Hospital Center Namur (Godinne), Yvoir, BelgiumDepartment of Clinical Hematology, Vrije Universiteit Brussel, Universitair Ziekenuis Brussel, Brussels, Belgium0Department of Clinical Hematology, ZNA Stuivenberg, Antwerp, Belgium1Belgian Hematology Society, Brussels, Belgium1Belgian Hematology Society, Brussels, Belgium2Department of Clinical Hematology, Ghent University Hospital, Ghent, BelgiumDepartment of Clinical Hematology, University Hospital Center and University of Liège, Liège, BelgiumIntroductionPoor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT.MethodsWe prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330).ResultsWithin 90 days post-MSC infusion, 53% (95% CI, 35 – 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 109/L, Hb > 80g/L and platelet count > 20 x 109/L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 109/L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 – 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention.DiscussionIn conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1106464/fullpoor graft functioncytopeniathrombocytopeniamesenchymal stromal cellsallogeneic stem cell transplantation |
spellingShingle | Sophie Servais Frédéric Baron Chantal Lechanteur Laurence Seidel Etienne Baudoux Alexandra Briquet Dominik Selleslag Johan Maertens Xavier Poire Wilfried Schroyens Carlos Graux Ann De Becker Pierre Zachee Aurélie Ory Julie Herman Tessa Kerre Yves Beguin Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis Frontiers in Immunology poor graft function cytopenia thrombocytopenia mesenchymal stromal cells allogeneic stem cell transplantation |
title | Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis |
title_full | Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis |
title_fullStr | Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis |
title_full_unstemmed | Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis |
title_short | Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis |
title_sort | multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation a multicenter prospective analysis |
topic | poor graft function cytopenia thrombocytopenia mesenchymal stromal cells allogeneic stem cell transplantation |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1106464/full |
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