Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review

Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review

Abstract Background Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD). Methods Based on our previous pil...

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Main Authors: Gérôme Lombardo, Chantal Lechanteur, Alexandra Briquet, Laurence Seidel, Evelyne Willems, Sophie Servais, Etienne Baudoux, Tessa Kerre, Pierre Zachee, Julie Herman, Audrey Janssen, Joséphine Muller, Frédéric Baron, Yves Beguin
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Stem Cell Research & Therapy
Subjects:
Allogeneic hematopoietic cell transplantation
Mesenchymal stromal cells
GVHD
Prevention
HLA mismatch
Online Access:https://doi.org/10.1186/s13287-024-04064-w
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Summary:Abstract Background Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD). Methods Based on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5–3 × 106/kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning. Results The study planned to include 120 patients to improve 1-year overall survival (OS) from 55 to 77% but was stopped after 9 years for low recruitment (n = 38). One-year OS was 74% in the MSC group and 80% in the placebo group. In multivariate analysis, the incidence of grade II-IV acute GVHD was significantly lower in patients receiving MSC (HR 0.332, 95% CI 0.124–0.890, p = 0.0284). No difference was observed in the incidences of chronic GVHD, infection or relapse, overall or progression-free survival at 1 year or long-term, or hematopoietic and immune reconstitution. Conclusions Despite premature study closure, the suggested beneficial effect of MSC co-transplantation for the prevention of acute GVHD in HLA-mismatched HCT warrants further investigation.
ISSN:1757-6512

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