Coinfusion of Mesenchymal Stromal Cells Facilitates Platelet Recovery Without Increasing Leukemia Recurrence in Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized, Controlled Clinical Study
Coinfusion of Mesenchymal Stromal Cells Facilitates Platelet Recovery Without Increasing Leukemia Recurrence in Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized, Controlled Clinical Study
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DOI：
10.1089/scd.2010.0447
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Huang, Xiaojun
中科院分区：
文献类型：
--
作者：
Liu, Kaiyan;Chen, Yuhong;Huang, Xiaojun
先前的研究表明，间充质基质细胞（MSC）可以增强造血干细胞的植入并调节宿主的免疫反应。然而，没有随机研究来证实这些结果。此外，由于间充质干细胞的免疫抑制特性，人们担心肿瘤复发的风险。我们进行了一项开放标签、随机 II 期临床研究，以评估半相合造血干细胞移植期间 MSC 混输（3-5x10(5) 个细胞/kg）的结果。 2007年6月至2008年6月，共有55名被诊断患有完全缓解的白血病的患者进入研究（治疗组27名，对照组28名）。没有发现与 MSC 输注相关的即时或长期毒副作用，两组之间白细胞和血小板植入的中位时间相当。然而，在100天内，与对照组相比，治疗组血小板浓度达到>50x10(9)细胞/L的时间明显更快（22天vs.28天；P=0.036）。与对照组相比，治疗组的基质衍生因子 1 α (SDF-1 α) 达到峰值浓度更快（第 8 天与第 16 天）。与对照组相比，MSC 治疗组的 SDF-1 α、血小板生成素 (TPO) 和白细胞介素 11 浓度也有所升高。治疗组和对照组2级以上急性移植物抗宿主病累计发生率分别为51.8%和38.9%（P=0.422），慢性移植物抗宿主病累计发生率分别为51.4%和74.1%（P=0.261）。截至 2010 年 3 月，即 2 年，MSC 治疗组的总生存率为 69.7%，对照组为 64.3%（P=0.737）。治疗组中有3名患者和对照组有2名患者出现血液学复发并死于白血病。
Previous studies have suggested that mesenchymal stromal cells (MSCs) enhance the engraftment of hematopoietic stem cells and modulate the host's immune response. However, there are no randomized studies to confirm these results. Moreover, there are some concerns about the risk of tumor recurrence because of the immunosuppressive property of MSCs. We conducted an open-label, randomized phase II clinical study to assess the outcome of MSC coinfusion (3-5x10(5) cells/kg) during haploidentical hematopoietic stem cell transplantation. From June 2007 to June 2008, a total of 55 patients who were diagnosed with leukemia in complete remission entered the study (27 in the treatment group and 28 in the control group). No immediate or long-term toxic side effects related to MSC infusion were noted, and the median times of white blood cell and platelet engraftment were comparable between the 2 groups. However, within 100 days, the time to a platelet concentration of >50x10(9) cells/L was markedly faster in the treatment group compared with the control group (22 days vs. 28 days; P=0.036). Stromal-derived factor-1 alpha (SDF-1 alpha) reached a peak concentration more rapidly in the treatment group compared with the control group (8th vs. 16th day). The concentrations of SDF-1 alpha, thrombopoietin (TPO), and interleukin-11 were also elevated in the MSC-treated group compared with the control group. The accumulative occurrence rate of acute graft-versus-host disease greater than grade 2 was 51.8% and 38.9% in the treatment and control groups (P=0.422), respectively, whereas the occurrence rate of chronic graft-versus-host disease was 51.4% and 74.1% (P=0.261), respectively. Through March 2010, which marked 2 years, the overall survival rate was 69.7% for the MSC-treated group and 64.3% for the control group (P=0.737). Three patients in the treatment group and 2 patients in the control group experienced a hematological relapse and died of leukemia.