单倍体造血干细胞移植治疗儿童非恶性疾病临床研究——单中心回顾性分析

Clinical study of haploidentical hematopoietic stem cell transplantation in the treatment of non-malignant diseases in children:a single-center retrospective analysis

目的探讨单倍体造血干细胞移植(haplo-HSCT)治疗儿童非恶性疾病(NMD)的临床疗效。方法回顾性分析2012年4月1日-2018年3月31日本中心收治的94例儿童NMD,均进行了haplo-HSCT,其中85例加第三方脐血。男72例,女22例。中位年龄5.4岁。预处理以白消安为基础。预防急性移植物抗宿主病(aGVHD)采用环孢霉素A、吗替麦考酚酯和甲氨蝶呤,于Old输注单倍体骨髓造血干细胞和第三方脐血,02d输注单倍体外周血造血干细胞,回输总单个核细胞中位数为13.5×10~8/kg,CD34^+细胞中位数为4.03×10~6/kg。结果中性粒细胞和血小板植入中位天数分别是+15d和+22d。Ⅰ~Ⅱ度和Ⅲ~Ⅳ度aGVHD发生率分别为40.4%和12.8%,8例出现慢性GVHD。CMV血症发生率54.3%;26例出现EBV血症,发生率达27.7%,4例进展为EBV相关移植后淋巴细胞增殖性疾病,予CD20单克隆抗体后控制。中位随访时间38个月,91例存活(90例无病存活,1例带病存活),死亡3例。5年OS和FFS分别为96.3%和87.4%。结论 Haplo-HSCT为一些NMD患儿争取治疗时机,疗效明确。

Objective To investigate the clinical efficacy of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)in the treatment of non-malignant diseases(NMD)in children.Methods From April 1 of 2012 to March 31of 2018,94 pediatric patients with NMD received haplo-HSCT in our hospital,of which 85 cases were added to third-party cord blood.All of them included 72 males and 22 females,median age was 5.4 years.The conditioning regimen was based on busulfan.The prophylaxis of acute graft versus host disease(aGVHD)consisted of cyclosporine,MMF and methotrexate.The patients received stem cells of the bone marrow from haploid donor and third-party umbilical cord blood on day 01 and the peripheral stem cells from haploid donor on day 02.The median dose of donor total mononuclear cells was 13.5×10^8/kg of recipient weight and CD34+cell counts was 4.03×10^6/kg of recipient weight.Results The median days of neutrophil and platelet implantation were day+15 and+22d after transplantation,respectively.The incidence rate of aGVHD were 40.43%for grade to gradeⅡ,and 12.8%for gradeⅢto gradeⅣ,respectively.Eight cases occurred chronic GVHD(cGVHD).The incidence rate of CMV viremia was 54.3%.Twenty-six cases occurred EBV viremia treated with rituximab,and the incidence rate of EBV viremia was 27.7%and 4 cases progressed to EBV-related post-transplant lymphoproliferation disorder(PTLD).The median follow-up was 38 months,91 patients survived,including 90 patients with disease free survival and 1 case of CGD with disease survival;Three patients died.The 5-year OS and FFS were 96.3%and 87.4%,respectively.Conclusions Haplo-HSCT can improve the opportunities of treatment for some children with NMD.