节点文献
遗传性骨髓衰竭综合征的诊断及造血干细胞移植治疗
Diagnosis and Hematopoietic Stem Cell Transplantation in Children with Inherited Bone Marrow Failure Syndromes
【作者】 李倩；
【导师】 陈静；
【作者基本信息】 上海交通大学 ， 儿科学（血液肿瘤科）（专业学位）， 2017， 博士
【摘要】 目的:分析儿童遗传性骨髓衰竭综合征(inherited bone marrow failure syndromes,IBMFS)的诊断及造血干细胞移植(hematopoietic stem cell transplantation,HSCT)治疗的结果,讨论相关诊疗进度。方法:1.对上海儿童医学中心血液肿瘤科确诊并接受HSCT治疗,并随访存档的IBMFS病例进行回顾性分析,存档资料包括临床特点、移植方案、移植物抗宿主病(graft versus host disease,GVHD)等。2.对第一部分中接受非亲缘HSCT的4例先天性角化不良(dyskeratosis congenita,DKC)病例进行分析。3.通过检索Pubmed,Embase,Web of Science,万方,中国知网和维普数据库等发表的有关HSCT治疗DKC的所有文献,根据设定的入排标准筛选文献,采用Stata12.0软件进行Meta分析比较同胞与非亲缘供体移植治疗DKC的疗效。结果:1.IBMFS患儿包括范可尼贫血12例、纯红细胞再生障碍性贫血7例、DKC 5例、先天性中性粒细胞减少伴胰腺功能不全综合征1例,接受了异基因HSCT治疗。其中干细胞来源包括外周血(n=20)和脐带血(n=5)。纯红细胞再生障碍性贫血接受了白消安为主的清髓性预处理,其余三种疾病的患儿接受了以氟达拉滨为主的减低剂量预处理。移植中位年龄4岁,移植过程中回输中位有核细胞数和CD34~+细胞数分别为14.4×10~8/kg和5.3×10~6/kg。粒细胞、血小板重建中位时间分别为为12和17天。中位随访27个月,仅一例植入失败。移植后2年生存率为96%。Ⅱ-Ⅲ级急性GVHD和慢性GVHD发生率分别为33.3%和16.7%,预处理强度是影响前者发生的唯一因素。2.4例DKC患儿接受了减低剂量预处理后HSCT治疗,干细胞来源于非亲缘供体外周血,均获得完全供体植入;其中2例发生Ⅱ-Ⅲ级急性GVHD,1例慢性GVHD。中位随访23.5个月,4例患儿均存活并保持非输血依赖,其中1例患儿的先天性指甲萎缩得到纠正。3.共纳入相关文献6篇(其中1篇即本研究),累积DKC病例63例。Meta分析显示,同胞与非亲缘HSCT相比,在急性和慢性GVHD发生率、植入成功率、3年无病生存率方面并无显著差异,但是前者较后者在5年无病生存率方面可能有一定优势。结论:基于疾病特点,选择合适的预处理方案是应用异基因造血干细胞移植治疗IBMFS患儿的关键。非亲缘供体是DKC移植治疗的有效干细胞来源。
【Abstract】 Objectives:The aim of this study was to analyze the clinical diagnosis and outcomes of hematolpoietic stem cell transplantation(HSCT)in children with inherited bone marrow failure syndromes(IBMFS).Methods:1.Clinical features,conditioning regimens and outcomes of HSCT in patients with IBMFS from Shanghai Children’s Medical Center were retrospectively reviewed.2.Four cases of dyskeratosis congenita(DKC)among 25 patients with IBMFS were discussed and analyzed in this part.3.All the literatures about HSCT on patients with DKC were searched through Pubmed,Embase,Web of Science,Wanfang,China Knowledge Network and Weibu database.The data was screened according to the standard of inclusion criteria.Meta analysis was conducted on HSCT of DKC from sibling and unrelated donors using Stata 12.0 software.Results:1.We report HSCT in 25 children with Fanconi anemia(FA,n=12),Diamond–Blackfan anemia(DBA,n=7)and dyskeratosis congenita(DKC,n=5)and Shwachman-Diamond syndrome(n=1)from Shanghai Children’s Medical Center.The graft source was peripheral blood stem cells(n=20)or cord blood stem cells(n=5).FA,DC and SDS patients received reduced-intensity conditioning,while DBA patients had myeloablative conditioning.The median numbers of infused mononuclear cells and CD34~+cells were 14.4×10~8/kg and 5.3×10~6/kg,respectively.The median time for neutrophil and platelet recovery was 12 and 17 days,respectively.There was one primary graft failure.During a median follow-up of 27 months(range,2–133 months),the overall survival in all patients was 95.8%.The incidence of gradeⅡ–Ⅲacute and chronic graft versus host disease(GVHD)was 29.2%and 16.7%,respectively.2.We report our experience in 4 children with DKC who underwent HSCT after a fludarabine-based reduced intensity conditioning.The graft source was unrelated peripheral blood stem cells.Two patients experienced gradeⅡ–Ⅲacute GVHD,and chronic GVHD was only observed in one patient.All four patients remained alive and transfusion-independent at the median follow-up of 23.5 months.Correction of previously existing physical defects was observed in one patients.3.Were included 6 reports(ours included),63 cases of HSCT in DKC in total.Meta-analysis showed that there was no significant difference in the incidence of acute and chronic GVHD,the rate of donor engraftment and the 3-year event-free survival rate between sibling and unrelated donors,but the former may have advantages over the latter on 5-year event-free survival rate.Conclusions:Choosing appropriate conditioning regimens based on the characteristics of disease is the key to successful allogeneic HSCT in children with IBMFS.The unrelated donor is an effective source of stem cells for DKC transplantation.