Treatment of post-allogeneic hematopoietic stem cell transplant cytopenias with sequential doses of multipotent mesenchymal stromal/stem cells.

MSC allogeneic hematopoietic transplantation bone marrow cytopenias mesenchymal stem cells mesenchymal stromal cells multipotent mesenchymal stromal/stem cells

Journal

Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309

Informations de publication

Date de publication:
21 Apr 2024
Historique:
received: 29 11 2023
revised: 08 04 2024
accepted: 15 04 2024
medline: 10 5 2024
pubmed: 10 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche. A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed. The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported. In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.

Sections du résumé

BACKGROUND AIMS OBJECTIVE
Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche.
METHODS METHODS
A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed.
RESULTS RESULTS
The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported.
CONCLUSIONS CONCLUSIONS
In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.

Identifiants

pubmed: 38727653
pii: S1465-3249(24)00612-1
doi: 10.1016/j.jcyt.2024.04.006
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Auteurs

Almudena Navarro-Bailón (A)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Faculty of Medicine, University of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain. Electronic address: almu_na@usal.es.

Miriam López-Parra (M)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain.

Álvaro Veiga-Vaz (Á)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain.

Eva María Villarón (EM)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain.

María Díez-Campelo (M)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Faculty of Medicine, University of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain; Biomedical Research Networking Center for Cancer (CIBERONC), ISCIII, Spain.

Ana África Martín (AÁ)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain.

Estefanía Pérez-López (E)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain.

Mónica Cabrero (M)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain.

Lourdes Vázquez (L)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Faculty of Medicine, University of Salamanca, Salamanca, Spain.

Lucía López-Corral (L)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Faculty of Medicine, University of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain; Biomedical Research Networking Center for Cancer (CIBERONC), ISCIII, Spain.

Fermín Sánchez-Guijo (F)

Hematology Department, Cell Therapy Area, IBSAL-University Hospital of Salamanca, Salamanca, Spain; Faculty of Medicine, University of Salamanca, Salamanca, Spain; Network Center for Regenerative Medicine and Cellular Therapy of Castilla y León, Spain; RICORS of Advanced Therapies (TERAV), ISCIII, Spain; Biomedical Research Networking Center for Cancer (CIBERONC), ISCIII, Spain.

Classifications MeSH