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单倍型相合造血干细胞与脐带间充质干细胞共移植治疗儿童血液系统恶性肿瘤的疗效与安全性

[Efficacy and Safety of Co-transplantation of Haploidentical-HSC with Umbilical Cord Mesenchymal Stem Cell in Children with Hematologic Malignancies].

作者信息

Kang Hui-Zhu, Zheng Xiao-Li, Wang Zhi-Dong, Han Dong-Mei, Ding Li, Yan Hong-Min, Wang Heng-Xiang

机构信息

Department of Hematology, General Hospital of Chinese Air Force, Beijing 100142, China.

Department of Hematology, General Hospital of Chinese Air Force, Beijing 100142, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Aug;25(4):1151-1157. doi: 10.7534/j.issn.1009-2137.2017.04.034.

DOI:10.7534/j.issn.1009-2137.2017.04.034
PMID:28823285
Abstract

OBJECTIVE

To analyse the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cell(UC-MSC) with haploidentical hematopoietic stem cell transplantation(hi-HSCT) in children with hematologic malignancy.

METHODS

The clinical data of 47 children undergoing hi-HSCT were retrospectively analyzed from November 2003 to November 2014, among them 34 patients received UC-MSC from October 2011 to November 2014, and another 13 patients without UC-MSC from November 2003 to September 2011. The median follow-up time was 20(0.5-67) months.

RESULTS

No adverse events were observed after the UC-MSC transplantation. The engraftment rate, the median neutrophils engraftment time and platelet engraftment time all were not significantly different between hi-HSCT and hi-HSCT+UC-MSCT(P>0.05). The three-years cumulative overall survival (70.6% vs 23.1%),(P=0.004), three-years cumulative disease-free survival(52.9% vs 0) (P=0), and early cytomegalovirus (CMV) viremia (91.2% vs 38.5%) (P=0) in UC-MSC+hi-HSCT group were statistically significantly higher than that in the conventional hi-HSCT group. The morbidity of aGVHD (44.1% vs 92.3%) (P=0.003), I-II aGVHD (26.5% vs 61.5%) (P=0.041) and transplantation-related mortality (11.8% vs 46.2%) (P=0.017) in UC-MSC+hi-HSCT group was statistically significantly lower than that in hi-HSCT group, however, the morbidity of III-IV aGVHD (17.6% vs 30.8%), cGVHD (26.5% vs 30.8%), HC (35.3% vs 7.7%), pulmonary infection (52.9% vs 46.2%) and relapse rate (32.4% vs 53.8%) were not statistically significantly different (P>0.05) between the 2 groups.

CONCLUSION

The application of umbilical cord mesenchymal stem cell in children undergoing hi-HSCT is safe, the UC-MSC can improve the overall survival, disease-free survival and reduce transplantation-related mortality. UC-MSC can reduce the morbidity of aGVHD, but increase the early infection of CMV, however it is nothing for the pulmonary infection and relapse in the children after hi-HSCT.

摘要

目的

分析脐带间充质干细胞(UC-MSC)与单倍体造血干细胞移植(hi-HSCT)联合移植治疗儿童血液系统恶性肿瘤的疗效及安全性。

方法

回顾性分析2003年11月至2014年11月期间接受hi-HSCT的47例儿童的临床资料,其中34例患者于2011年10月至2014年11月接受了UC-MSC移植,另外13例患者于2003年11月至2011年9月未接受UC-MSC移植。中位随访时间为20(0.5-67)个月。

结果

UC-MSC移植后未观察到不良事件。hi-HSCT组与hi-HSCT+UC-MSCT组之间的植入率、中性粒细胞中位植入时间和血小板植入时间均无显著差异(P>0.05)。UC-MSC+hi-HSCT组的三年累积总生存率(70.6%对23.1%),(P=0.004),三年累积无病生存率(52.9%对0)(P=0),以及早期巨细胞病毒(CMV)病毒血症(91.2%对38.5%)(P=0)在统计学上显著高于传统hi-HSCT组。UC-MSC+hi-HSCT组的急性移植物抗宿主病(aGVHD)发病率(44.1%对92.3%)(P=0.003)、I-II级aGVHD(26.5%对61.5%)(P=0.041)和移植相关死亡率(11.8%对46.2%)(P=0.017)在统计学上显著低于hi-HSCT组,然而,III-IV级aGVHD发病率(17.6%对30.8%)、慢性移植物抗宿主病(cGVHD)(26.5%对30.8%)、出血性膀胱炎(HC)(35.3%对7.7%)、肺部感染(52.9%对46.2%)和复发率(32.4%对53.8%)在两组之间无统计学显著差异(P>0.05)。

结论

脐带间充质干细胞在接受hi-HSCT的儿童中的应用是安全的,UC-MSC可提高总生存率、无病生存率并降低移植相关死亡率。UC-MSC可降低aGVHD的发病率,但增加CMV的早期感染,然而对hi-HSCT后儿童的肺部感染和复发无影响。

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引用本文的文献

1
Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.间充质干细胞共输注在异基因造血干细胞移植中的疗效和安全性:系统评价和荟萃分析。
Stem Cell Res Ther. 2021 Apr 20;12(1):246. doi: 10.1186/s13287-021-02304-x.
2
Pre-infusion single-dose mesenchymal stem cells promote platelet engraftment and decrease severe acute graft versus host disease without relapse in haploidentical peripheral blood stem cell transplantation.预处理单次输注间充质干细胞可促进血小板植入,并降低单倍体外周血造血干细胞移植后严重急性移植物抗宿主病而不复发。
J Int Med Res. 2020 May;48(5):300060520920438. doi: 10.1177/0300060520920438.