State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China.
National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, 300020, China.
BMC Pediatr. 2021 Feb 27;21(1):102. doi: 10.1186/s12887-021-02562-x.
Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA).
We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 10/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone.
Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153).
Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).
骨髓间充质干细胞（BM-MSCs）在增殖和分化方面的缺陷与再生障碍性贫血（AA）的病理生理学有关。输注脐带间充质干细胞（UC-MSCs）可能会改善儿童重型再生障碍性贫血（SAA）的免疫抑制治疗（IST）疗效。
我们开展了一项由研究者发起的、开放性标签的、前瞻性 IV 期临床试验，以评估同种异体 UC-MSCs 联合标准 IST 治疗新诊断的 SAA 儿科患者的安全性和疗效。在间充质干细胞（MSC）组中，兔抗胸腺细胞球蛋白（ATG）给药后第 14 天开始每周静脉注射 1×10/kg 的 UC-MSCs，共 3 周。将接受 UC-MSCs 输注的患者的临床结果和不良事件与接受标准 IST 单独治疗的同期对照组患者进行比较。
9 例中位年龄为 4 岁的患者被纳入 MSC 组，而另 9 例儿童 SAA 的数据被分析为对照组。MSC 组有 4 例（44%）患者发生过敏反应，与兔 ATG 相关。与对照组相比，MSC 组的血细胞计数改善和 IST 后 T 淋巴细胞变化均无统计学意义（均 p>0.05），MSC 组有 1 例（11%）患者和对照组有 2 例（22%）患者在 IST 后 90 天达到部分缓解（PR）。中位随访 48 个月后，两组均未发生克隆演变。两组 4 年总生存率（OS）分别为 88.9%±10.5%，MSC 组 4 年无失败生存率（FFS）低于对照组（38.1%±17.2%比 66.7%±15.7%，p=0.153）。
IST 联合 UC-MSCs 治疗 SAA 儿童是安全的，但不一定能提高早期反应率和长期预后。这项临床试验在 ClinicalTrials.gov 注册，标识符为 NCT02218437（2013 年 10 月注册）。
