儿童晚期神经母细胞瘤自身造血干细胞移植疗效评估  

Evaluation of the outcomes of autologous hematopoietic stem cells transplantation on the treatment of children with advanced neuroblastoma

作　　者：陈静[1] 沈小钰[1] 汤静燕[1] 薛惠良[1] 潘慈[1] 董璐[1] 江华[1] 周敏[1] 叶启东 罗长缨[1] 顾龙君[1] 王耀平[1] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心血液/肿瘤科,上海200127

出　　处：《中国循证儿科杂志》2009年第2期117-122,共6页Chinese Journal of Evidence Based Pediatrics

基　　金：上海市浦东新区科技发展基金:PKJ2004-82

摘　　要：目的评价自身造血干细胞移植(ASCT)和CD34+细胞分选的ASCT对晚期神经母细胞瘤(NB)的疗效。方法回顾性分析2001年6月至2007年4月在上海交通大学医学院附属上海儿童医学中心诊断为Ⅲ、Ⅳ期NB并完成治疗随访8个月以上患儿的临床资料,比较传统化疗与ASCT和CD34+细胞未分选移植与分选移植的疗效。用荧光定量PCR方法检测CD34+细胞分选前后酪氨酸羟化酶(TH)mRNA表达,监测NB的微小残留(MRD),并评估分选效果。结果55例NB患儿入组,其中Ⅲ期14例,Ⅳ期41例。Ⅲ期中的9/14例和Ⅳ期中的18/41例接受传统化疗;Ⅲ期中的5/14例和Ⅳ期中的23/41例接受ASCT。Ⅳ期13/23例接受ASCT治疗患儿移植物经CliniMACS行CD34+细胞分选处理。所有移植患儿均以卡铂、依托泊苷和美法仑行预处理,平均采得有核细胞(7.1±2.5)×108·kg-1,CD34+细胞(4.0±1.5)×106·kg-1,无一例因移植相关并发症死亡。随访患儿的生存时间及复发率:①Ⅲ期NB:化疗组平均随访33.5个月,3/9例(33%)复发;移植组平均随访37.0个月,1/5例(20%)复发,两组的中位无病生存时间差异无统计学意义,(37.0±15.7)个月vs(18.0±29.9)个月,P=0.446。②Ⅳ期NB:化疗组平均随访20个月,13/18例(72%)复发;移植组平均随访29个月,14/23例(61%)复发,两组的中位无病生存时间差异有统计学意义,(24.0±5.4)个月vs(36.0±2.8)个月,P=0.006。③CD34+细胞分选移植:未分选组平均随访27.8个月,7/10例(70%)复发;CD34+细胞分选组平均随访30.0个月,7/13例(54%)复发,两组的中位无病生存时间差异无统计学意义,(34.0±11.8)个月vs(36.0±5.1)个月,P=0.722。4例移植患儿CD34+细胞分选前后的标本同时进行THMRD检测,结果显示移植前TH阳性的2例标本经分选后全部转阴。结论ASCT能显著延长Ⅳ期NB患儿的长期生存时间,但对Ⅲ期NB患儿的疗效不显著。CD34+细胞分选能达到纯化NB细胞的作用,但可能因病例数较少,尚不能显示出ASCT临床优Objective High-risk neuroblastoma （NB） is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The aims of this study were to evaluate the prognosis of children with advanced NB and to compare the outcomes of unpurged autologous hematopoietic stem-cell （ASCT） and CD34 ^＋ selected stem-cell transplantation with traditional chemotherapy alone in stage Ⅲ and Ⅳ NB. Methods A retrospective analysis of stage Ⅲ and Ⅳ NB children from Jun 2000 to Apr 2007 was performed. A sensitive FQ-PCR method to test the expression of tyrosine hydroxylase was used to monitor minimal residual disease （ MRD ） and to evaluate the purity of CD34 ^＋ selected transplantation. Results Totally 55 NB patients finished chemotherapy and were enrolled in this study with 14 in stage Ⅲ and 41 in stage Ⅳ. In stage Ⅲ：9/14 NB patients didn＇t receive transplant （chemotherapy group） and 5/14 receive ASCT （transplant group）. In stage Ⅳ： 18/41 NB patients were in chemotherapy group and 23/41 were in transplant group. In stage Ⅳ transplant group： 13/23 NB patients received CliniMACS based CD34 ＋ selected stem cells transplantation while 10/23 received unpnrged autologous transplant. For ASCT： all NB patients received the conditioning regimen including carboplatin 300 mg · m^ -2 ·d^-1 ×4d ＋ etoposide （VP16） 160mg·m^-2 ·d^-1 ×4 d ＋ melphalan 180-210 mg· m^-2 . The mean number of total nuclear cells and CD34^＋ cells from autograft was （7.1 ± 2.5 ） × 10^8 ·kg^- 1 and （4.0 ± 1.5 ） × 10^6 ·kg^- 1. The mean time for the neutrophile recovering over 0.5 × 10^9 ·L ^- 1 was （ 10.5 ±5.7 ） days and for the platelet recovering over 2.0 × 10^9 ·L ^-1 was （16.8±9.4） days with average 2 units of packed red blood cells and 4 units of platelet were transfused during

关 键 词：儿童 晚期神经母细胞瘤 自体造血干细胞移植 CD34+细胞分选 

分 类 号：R739.41[医药卫生—肿瘤]