单倍体相合造血干细胞移植联合脐带间充质干细胞输注治疗儿童恶性血液病的临床研究  

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

作　　者：康慧珠 郑晓丽[1] 王志东[1] 韩冬梅[1] 丁丽[1] 闫洪敏[1] 王恒湘[1] 

机构地区：[1]中国人民解放军空军总医院血液科,北京100142

出　　处：《中国实验血液学杂志》2017年第4期1151-1157,共7页Journal of Experimental Hematology

基　　金：首都卫生发展科研专项(首发2014-2-5122);首都临床特色应用研究与成果推广(Z151100004015016)

摘　　要：目的:探讨脐带间充质干细胞(UC-MSC)在儿童单倍体相合造血干细胞移植(haploidentical-HSCT,hiHSCT)中应用的安全性及疗效。方法:回顾性分析了本中心2003年11月至2014年11月接受hi-HSCT的47例儿童高危或复发的恶性血液病患者的临床资料,根据有无联合输注UC-MSC,将病例分为2组,一组为传统hi-HSCT组,从2003年11月至2011年9月共13例;另一组为UC-MSC+hi-HSCT组,从2011年10月到2014年11月共34例。中位随访时间为20(0.5-67)个月。结果:UC-MSC输注无不良反应发生。2组患者在粒系及血小板植入率、植入时间方面并无统计学差异(P>0.05)。UC-MSC+hi-HSCT组和hi-HSCT组,3年累积生存(OS)分别为70.6%和23.1%(P=0.004)、无病生存率(DFS)分别为52.9%和0(P=0)、移植相关死亡率(TRM)分别为11.8%和46.2%(P=0.017),差异均具有统计学意义;而RR分别为32.4%和53.8%(P>0.05),不具有统计学意义。早期巨细胞病毒(CMV)血症发病率分别为91.2%和38.5%(P=0),急性移植物抗宿主病(a GVHD)发病率分别为44.1%和92.3%(P=0.003),Ⅰ-Ⅱa GVHD发病率分别为26.5%和61.5%(P=0.041),差异均有统计学意义。而Ⅲ-Ⅳa GVHD发病率分别为17.6%和30.8%、慢性移植物抗宿主病(c GVHD)发病率分别为26.5%和30.8%,出血性膀胱炎(HC)分别为35.3%和7.7%,肺部感染发生率分别为52.9%和46.2%,差异均无统计学意义(P>0.05)。结论:UC-MSC在儿童中应用是安全的,能提高hi-HSCT后3年OS、DFS,降低移植相关死亡率(TRM)。在儿童hiHSCT中,UC-MSC能减轻a GVHD发生率,但增加了早期CMV血症发病率,对造血植入、肺部感染及疾病复发无影响。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 hiHSCT 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-HSCTgroup 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 UCMSC 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

关 键 词：单倍体造血干细胞移植 儿童恶性血液病 脐带间充质干细胞 

分 类 号：R457.7[医药卫生—治疗学]