单倍型异基因造血干细胞与脐带间充质干细胞联合移植进行性肌营养不良症15例临床观察

目的]探讨脐带间充质干细胞与单倍型异基因造血干细胞联合移植的安全性、疗效及对术后造血重建、移植物抗宿主病（GVHD）等并发症的影响.方法]选择进行性肌营养不良症男性儿童15例采用环磷酰胺（ Cy） ＋马利兰（ Bu） ＋氟达拉宾（ Flu）方案预处理后行单倍型异基因造血干细胞移植术,移植当天输注造血干细胞后1 h给予体外扩增的第三方脐带间充质干细胞静脉输注,输注细胞数量为（1.81～4.52）×106/kg中位数量（3.17±1.36）×106/kg],观察术后造血重建、造血干细胞植入、GVHD等移植并发症及严重程度.结果]15例患者均造血重建,中性粒细胞大于0.5×109/L时间为6～15 d（平均8.87 d）,血小板大于20×109/L的时间6～13 d（平均11.4 d）;移植后30 d经短串联重复序列- 聚合酶链反应（STR-PCR）检测显示所有患者均为完全供者型植入;4例患者出现Ⅱ～Ⅲ度急性移植物抗宿主病（占26.7%）,3例患者出现巨细胞病毒感染（占20%）,并发出血性膀胱炎4例（占26.7%）;平均随访时间228 （60～710）d,所有患者均存活,且病情稳定.结论]联合脐带间充质干细胞（UC-MSC）的单倍型异基因造血干细胞移植成功率高;充质干细胞（MSC）对造血重建有促进作用,可减轻GVHD及其他移植相关并发症.

Clinical Observation of Haplotype Allogenic Hematopoietic Stem Cell and Umbilical Cord Mesenchymal Stem Cell Transplantation for the Treatment of 15 Patients with Progressive Muscular Dystrophy

Obieetive]To primarily explore the safety and effectiveness of haplotype allogenic hematopoi- etic stem cell（HSC） combined with umbilical cord mesenchymal stem cell（UC-MSC） transplantation and its influence on hematopoietic reconstruction and complications such as graft versus host disease （GVHD） after transplantation. Methods] Fifteen male children with Duchenne muscular dystrophy（DMD） received HSC transplantation after pretreatment with cyclophosphamide（Cy）＋busulphan（Bu）＋fludarabine（Flu）. At lh after the transfusion of HSC on the day of transplantation, the amplified UC-MSC from the third party was intravenously injected. The number of UC-MSC was （1.81-4.52）×10^6/kg with the median of （3.17± 1.36） ×10^6/kg. H ematopoietic reconstruction, HSC implantation, complications such as GVHD and severity after transplantation were observed. Results] All of 15 patients achieved hematopoietic reconstruction. The duration with neutrophil number more than 0.5 ×10^9/L was 6- 15d with the median of 8.87d. The duration with platelet number more than 20×10^9/L was 6-13d with the median of 11.4d. STR-PCR showed that all patients were completely implanted by donor at 30d after transplantation. Four patients had grade Ⅱ～Ⅲ GVHD （26. 70/00）. Three patients had cytomegalovirus infection（20%）. Four patients were complicated by hemorrhagic cystitis（26.7%）. The follow up time was 60-710 d with the average of 228d. All patients survived and had stable status. Conclusion] Haplotype allogenic HSC combined with UC-MSC transplantation has high successful rate. MSC can promote hematopoietic reconstruction and relieve GVHD as well as other graft-related complications.