第三方骨髓来源间充质干细胞治疗异基因造血干细胞移植后难治性迟发性出血性膀胱炎20例临床研究  

Clinical study of mesenchymal stem cells from third-party donors in the treatment of refractory late onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplanation

作　　者：赵珂[1] 黄芬[1] 陈小湧 昌媛 许娜[1] 史鹏程[1] 刘慧[1] 孙竞[1] 项鹏[2] 刘启发[1] 范志平[1] Zhao Ke;Huang Fen;Chen Xiaoyong;Chang Yuan;Xu Na;Shi Pengcheng;Liu Hui;Sun Jing;Xiang Peng;Liu Qifa;Fan Zhiping(Department of Hematology,Nanfang Hospital,Southern Medical University,Gangzhou 510515,China;Center for Stem Cell Biology and Tissue Engineering,Sun Yat-Sen University,Guangzhou 510080,China)

机构地区：[1]南方医科大学南方医院血液科,广州510515 [2]中山大学干细胞与组织工程研究中心,广州510120

出　　处：《中华血液学杂志》2022年第6期488-493,共6页Chinese Journal of Hematology

基　　金：国家重点研发计划(2017YFA105500、2017YFA0105504、2017YFA0105503);广东省重点领域研发计划(2019B020236004);广东省自然科学基金博士启动项目(2017A030310103)。

摘　　要：目的观察第三方骨髓来源间充质干细胞(MSC)治疗异基因造血干细胞移植(allo-HSCT)后难治性迟发性出血性膀胱炎(LOHC)的疗效和安全性.方法回顾性分析2018年7月至2020年6月allo-HSCT后发生难治性LOHC 20例患者在常规治疗基础上联合第三方骨髓来源MSC治疗.MSC以每次1×10^(6)/kg、每周1次输注,直至症状改善或连用4次无效停用.在MSC治疗前及治疗后第8周应用定量PCR法检测患者尿液标本中BK病毒(BKV)、JC病毒(JCV)、巨细胞病毒(CMV).结果①20例难治性LOHC患者中,男15例、女5例,中位年龄35(15~56)岁;急性淋巴细胞白血病(ALL)5例,急性髓系白血病(AML)9例,骨髓增生异常综合征(MDS)5例,母细胞性浆细胞样树突细胞瘤(BPDCN)l例;HLA全相合移植4例,HLA不全相合移植16例.②MSC输注中位次数为3(2~8)次.17例患者获得完全缓解,1例获得部分缓解,总缓解率为90.0%.移植后中位随访397.5(39~937)d,13例存活、7例死亡,死亡原因包括急性GVHD 1例、感染5例、血栓性微血管病(TMA)1例.③MSC输注后第8周尿BKV-DNA及CMV-DNA拷贝数较治疗前显著降低(11342.1×10^(8)拷贝/L对5.2×10^(8)拷贝/L,P=0.016;3170.0×10^(4)拷贝/L对0.2×10^(4)拷贝/L,P=0.006),而JCV-DNA与治疗前相比无明显改变(P=0.106).④未发生MSC输注相关不良反应.结论第三方骨髓来源MSC对allo-HSCT后难治性LOHC具有显著疗效且安全性良好.Objective To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells(MSCs)in the treatment of refractory delayed hemorrhagic cystitis(LOHC)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors’bone marrow(BM).MSCs were given intravenously at a dose of 1×10^(6) cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times.BK viruria(BKV)-DNA,JC viruria(JCV)-DNA,and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion.Results①Of the 20 patients with refractory LOHC,15 were males,and 5 were females,and the median age was 35(15-56)years.There were 5 cases of acute lymphoblastic leukemia(ALL),9 cases of acute myeloid leukemia(AML),5 cases of myelodysplastic syndrome(MDS),and 1 case of maternal plasma cell like dendritic cell tumor(BPDCN).There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation.②The median number of MSC infusions for each patient was 3(range:2-8).Seventeen patients achieved complete response,and one had a partial response after treatment.The overall response rate was 90%.Over a median follow-up period of 397.5 days(range 39-937 days)post-transplantations,13 patients survived,and 7 died.The causes of death included aGVHD(1 case),infections(5 cases),and TMA(1 case).③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment(11342.1×10^(8) copies/L vs 5.2×10^(8) copies/L,P=0.016;3170.0×10^(4) copies/L vs 0.2×10^(4) copies/L,P=0.006,respectively),while JCV-DNA did not significantly differ when compared to before treatment(P=0.106).④No adverse reactions related to MSC infusion occurred in any of the 20 patients.Conclusion Third-party bone marrow-derived MSC has significant efficacy and good

关 键 词：难治性迟发性出血性膀胱炎 异基因造血干细胞移植 间充质干细胞 

分 类 号：R457.7[医药卫生—治疗学] R694.3[医药卫生—临床医学]