难治性或复发性再生障碍性贫血患者的异基因间充质基质细胞静脉输注

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

作者信息

Clé Diego V, Santana-Lemos Barbara, Tellechea Maria Florencia, Prata Karen L, Orellana Maristela D, Covas Dimas T, Calado Rodrigo T

机构信息

Department of Internal Medicine, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil; Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.

出版信息

Cytotherapy. 2015 Dec;17(12):1696-705. doi: 10.1016/j.jcyt.2015.09.006.

DOI:10.1016/j.jcyt.2015.09.006

PMID:26589752

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 × 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.

摘要