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Randomized Controlled Trial
. 2024 Dec 3;15(1):461.
doi: 10.1186/s13287-024-04064-w.

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

Gérôme Lombardo  1 , Chantal Lechanteur  2 , Alexandra Briquet  2 , Laurence Seidel  3 , Evelyne Willems  1 , Sophie Servais  1 , Etienne Baudoux  2 , Tessa Kerre  4 , Pierre Zachee  5 , Julie Herman  1 , Audrey Janssen  1 , Joséphine Muller  1 , Frédéric Baron  1 , Yves Beguin  6   7
Affiliations
Randomized Controlled Trial

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

Gérôme Lombardo et al. Stem Cell Res Ther. .

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.

Keywords: Allogeneic hematopoietic cell transplantation; GVHD; HLA mismatch; Mesenchymal stromal cells; Prevention.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The protocol “Co-transplantation of mesenchymal stem cells and HLA-mismatched allogeneic hematopoietic cells after nonmyeloablative conditioning: a phase II randomized double-blind study” was approved centrally by the “Comité d’Ethique Hospitalo-Facultaire Universitaire de Liège” on 6 July 2010 (file 2010/16) as well as by the ethics committees of all participating centers and the study was conducted in accordance with the Declaration of Helsinki. Before participating in the study, all patients (or their legal representatives if minors) signed an informed consent form. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overall survival in MSC compared to placebo patients
See this image and copyright information in PMC

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