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

Author(s)

Cle, Diego V. ^{[1, 2]} ; Santana-Lemos, Barbara ^{[1, 2]} ; Tellechea, Maria Florencia ^[1] ; Prata, Karen L. ^[1] ; Orellana, Maristela D. ^[1] ; Covas, Dimas T. ^{[1, 2]} ; Calado, Rodrigo T. ^{[1, 2]}

Affiliation

^[1] Sao Paulo Res Fdn FAPESP, Ctr Cell Based Therapy, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeir Preto Sch Med, Dept Internal Med, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: CYTOTHERAPY; v. 17, n. 12, p. 1696-1705, DEC 2015.
• Web of Science Citations: 9

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 x 10(6) 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. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC