Clé Diego V, Santana-Lemos Barbara, Tellechea Maria Florencia, Prata Karen L, Orellana Maristela D, Covas Dimas T, Calado Rodrigo T
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.
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.
Cytotherapy. 2015 Dec;17(12):1696-705. doi: 10.1016/j.jcyt.2015.09.006.
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.
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.
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.
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.
对于抗胸腺细胞球蛋白（ATG）和环孢素治疗无效的再生障碍性贫血（AA）患者，第二疗程免疫抑制治疗仅在四分之一至三分之一的病例中取得成功。
我们开展了一项1/2期研究，纳入9例难治性或复发性AA患者，评估在标准兔ATG和环孢素基础上，每周静脉输注2至5次异体非人类白细胞抗原匹配的骨髓间充质基质细胞（MSC）（中位数为2.7×10⁶细胞/kg/次；范围为1.3 - 4.5）的疗效。
中位随访20个月后，未观察到与输注相关的不良事件，但有4例患者因心力衰竭、细菌或侵袭性真菌感染死亡；仅2例患者在6个月时获得部分血液学缓解。输注后30、90或180天，我们未能通过荧光原位杂交或可变数目串联重复序列在患者骨髓中证实有任何MSC植入。
AA患者输注异体MSC是安全的，但未改善临床血液学反应或在受者骨髓中植入。本研究已在clinicaltrials.gov注册，标识符：NCT01297972。
