Adipose tissue-derived mesenchymal stromal cells as part of therapy for chronic graft-versus-host disease: A phase I/II study.

Abstract

BACKGROUND AIMS:

Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD.

METHODS:

Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy.

RESULTS:

Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells.

DISCUSSION:

AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.

• Authors: Manuel Jurado, Claudia De La Mata, Antonio Ruiz-García, Elisa López-Fernández, Olga Espinosa, María José Remigia, Lucía Moratalla, Rosa Goterris, Paloma García-Martín, Francisco Ruiz-Cabello, Sebastián Garzón, María Jesús Pascual, Ildefonso Espigado, Carlos Solano
• Journal: Cytotherapy (Cytotherapy) Vol. 19 Issue 8 Pg. 927-936 (08 2017) ISSN: 1477-2566 [Electronic] England
• PMID: 28662983 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Tumor Necrosis Factor-alpha
• Cyclosporine
• Prednisone

Topics

• Adipose Tissue (cytology)
• Adult
• Cyclosporine (therapeutic use)
• Female
• Graft vs Host Disease (therapy)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Killer Cells, Natural
• Male
• Mesenchymal Stem Cell Transplantation (adverse effects, methods)
• Mesenchymal Stem Cells
• Middle Aged
• Prednisone (therapeutic use)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (metabolism)