Intravenous infusion of allogeneic mesenchymal stromal cells in refractory or relapsed aplastic anemia

Abstract Background aims For patients with aplastic anemia (AA) who are refractory to anti-thymocyte globulin (ATG) and cyclosporine, a second course of immunosuppression is successful in only one-fourth to one-third of cases. Methods We conducted a phase 1/2 study to evaluate the addition of two to...

Full description

Saved in:
Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2015-12, Vol.17 (12), p.1696-1705
Main Authors: Clé, Diego V, Santana-Lemos, Barbara, Tellechea, Maria Florencia, Prata, Karen L, Orellana, Maristela D, Covas, Dimas T, Calado, Rodrigo T
Format: Article
Language:English
Subjects:
Adult
Advanced Basic Science
Anemia, Aplastic - therapy
Antilymphocyte Serum - therapeutic use
aplastic anemia
Cyclosporine - therapeutic use
Female
Humans
Immunologic Factors - therapeutic use
immunosuppression
Immunosuppression - methods
Immunosuppressive Agents - therapeutic use
In Situ Hybridization, Fluorescence
Infusions, Intravenous
Male
Mesenchymal Stem Cell Transplantation - adverse effects
mesenchymal stromal cell engraftment
Mesenchymal Stromal Cells
Middle Aged
Other
Transplantation, Homologous
Treatment Outcome
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background aims For patients with aplastic anemia (AA) who are refractory to anti-thymocyte globulin (ATG) and cyclosporine, a second course of immunosuppression is successful in only one-fourth to one-third of cases. Methods We conducted a phase 1/2 study to evaluate the addition of two to five weekly intravenous infusions of allogeneic unrelated non–human leukocyte antigen–matched bone marrow–derived mesenchymal stromal cells (MSCs) (median, 2.7 × 106 cells/kg/infusion; range, 1.3–4.5) to standard rabbit ATG and cyclosporine in nine patients with refractory or relapsed AA. Results After a median follow-up of 20 months, no infusion-related adverse event was observed, but four deaths occurred as the result of heart failure and bacterial or invasive fungal infections; only two patients achieved partial hematologic responses at 6 months. We failed to demonstrate by fluorescence in situ hybridization or variable number tandem repeat any MSC engraftment in patient marrow 30, 90 or 180 days after infusions. Conclusions Infusion of allogeneic MSCs in AA is safe but does not improve clinical hematologic response or engraft in recipient bone marrow. This study was registered at clinicaltrials.gov , identifier: NCT01297972.
ISSN:1465-3249
1477-2566
DOI:10.1016/j.jcyt.2015.09.006