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

• Published in: Cytotherapy (Oxford, England) England), 2024-08, Vol.26 (8), p.806-812
• Main Authors: Navarro-Bailón, Almudena, López-Parra, Miriam, Veiga-Vaz, Álvaro, Villarón, Eva María, Díez-Campelo, María, Martín, Ana África, Pérez-López, Estefanía, Cabrero, Mónica, Vázquez, Lourdes, López-Corral, Lucía, Sánchez-Guijo, Fermín
• Format: Article
• Language: English
• Subjects: allogeneic hematopoietic transplantation; bone marrow; cytopenias; mesenchymal stem cells; mesenchymal stromal cells; MSC; multipotent mesenchymal stromal/stem cells
• ISSN: 1465-3249; 1477-2566; 1477-2566
• DOI: 10.1016/j.jcyt.2024.04.006

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.