Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis

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

doi:10.3389/fimmu.2023.1106464

Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis

Front Immunol. 2023 Feb 1:14:1106464. doi: 10.3389/fimmu.2023.1106464. eCollection 2023.

Authors

Sophie Servais¹, Frédéric Baron¹, Chantal Lechanteur², Laurence Seidel³, Etienne Baudoux², Alexandra Briquet², Dominik Selleslag⁴, Johan Maertens⁵, Xavier Poire⁶, Wilfried Schroyens⁷, Carlos Graux⁸, Ann De Becker⁹, Pierre Zachee¹⁰, Aurélie Ory¹¹, Julie Herman¹¹, Tessa Kerre¹², Yves Beguin¹

Affiliations

¹ Department of Clinical Hematology, University Hospital Center and University of Liège, Liège, Belgium.
² Laboratory of Cell and Gene Therapy, University Hospital Center and University of Liège, Liège, Belgium.
³ Department of Biostatistics, SIMÉ, University Hospital Center and University of Liège, Liège, Belgium.
⁴ Department of Clinical Hematology, AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium.
⁵ Department of Clinical Hematology, University Hospital Leuven, Leuven, Belgium.
⁶ Department of Clinical Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
⁷ Department of Clinical Hematology, Antwerp University Hospital, Edegem, Belgium.
⁸ Department of Clinical Hematology, Université Catholique de Louvain, University Hospital Center Namur (Godinne), Yvoir, Belgium.
⁹ Department of Clinical Hematology, Vrije Universiteit Brussel, Universitair Ziekenuis Brussel, Brussels, Belgium.
¹⁰ Department of Clinical Hematology, ZNA Stuivenberg, Antwerp, Belgium.
¹¹ Belgian Hematology Society, Brussels, Belgium.
¹² Department of Clinical Hematology, Ghent University Hospital, Ghent, Belgium.

Abstract

Introduction: Poor 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.

Methods: We 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).

Results: Within 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.

Discussion: In 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.

Keywords: allogeneic stem cell transplantation; cytopenia; mesenchymal stromal cells; poor graft function; thrombocytopenia.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Graft vs Host Disease*
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells*
Transplantation, Homologous / adverse effects

Grants and funding

YB and FB are Senior Research Associate at the FNRS. SS is Postdoctoral Researcher at the Belgian Foundation against Cancer (FBC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.