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中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (4) : 485 -491. doi: 10.3877/cma.j.issn.1673-5250.2015.04.011

所属专题: 文献

论著

造血干细胞移植治疗儿童高危及复发急性淋巴细胞白血病的临床研究
黄科, 方建培*(), 周敦华, 黎阳, 陈纯, 郭海霞, 徐宏贵, 薛红漫, 翁文骏, 黄绍良   
  1. 510120 广州,中山大学附属孙逸仙纪念医院儿科
  • 收稿日期:2015-01-09 修回日期:2015-05-02 出版日期:2015-08-01
  • 通信作者: 方建培

Clinical study of hematopoietic stem cell transplantation for high-risk and relapsed childhood acute lymphoblastic leukemia

Ke Huang, Jianpei Fang*(), Dunhua Zhou, Yang Li, Chun Chen, Haixia Guo, Honggui Xu, Hongman Xue, Wenjun Weng, Shaoliang Huang   

  1. Department of Pediatrics, the SUN Yat-sen Memorial Hospital, SUN Yat-sen University, Guangzhou 510120, Guangdong Province, China
  • Received:2015-01-09 Revised:2015-05-02 Published:2015-08-01
  • Corresponding author: Jianpei Fang
引用本文:

黄科, 方建培, 周敦华, 黎阳, 陈纯, 郭海霞, 徐宏贵, 薛红漫, 翁文骏, 黄绍良. 造血干细胞移植治疗儿童高危及复发急性淋巴细胞白血病的临床研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2015, 11(4): 485-491.

Ke Huang, Jianpei Fang, Dunhua Zhou, Yang Li, Chun Chen, Haixia Guo, Honggui Xu, Hongman Xue, Wenjun Weng, Shaoliang Huang. Clinical study of hematopoietic stem cell transplantation for high-risk and relapsed childhood acute lymphoblastic leukemia[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(4): 485-491.

目的

探讨影响高危及复发急性淋巴细胞白血病(ALL)患儿造血干细胞移植(HSCT)临床疗效的相关因素。

方法

选择2001年4月至2013年5月在中山大学附属孙逸仙纪念医院接受异基因HSCT(allo-HSCT)的34例高危及复发ALL患儿的临床病历资料为研究对象。其中B细胞型ALL(B-ALL)为28例,T细胞型ALL(T-ALL)为6例;21例为高危ALL首次完全缓解(CR1),13例为ALL复发后第2次CR(CR2)。按照接受allo-HSCT供体的不同,将其分为全相合同胞供体外周血干细胞移植(MSD-PBSCT)者(5例),非血缘相关供体脐血移植(UD-UCBT)者(11例),非血缘相关供体外周血干细胞移植(UD-PBSCT)者(18例)。allo-HSCT的预处理方案为:以白消安(BU)+环磷酰胺(CY)为基础,加用氟达拉宾(Flud),接受非血缘相关供体(UD)者预处理时,加用抗人胸腺细胞球蛋白(ATG)。本研究遵循的程序符合本院人体试验委员会制定的伦理学标准,得到该委员会批准,并与受试对象监护人签署临床研究知情同意书。

结果

本组34例患儿接受allo-HSCT后,30例成功植入患儿中,急性移植物抗宿主疾病(aGVHD)发生率为33.3%(10/30)。本组其中Ⅲ~Ⅳ度aGVHD发生率为16.7%(5/30),接受UD-PBSCT患儿的aGVHD发生率明显高于接受MSD-PBSCT及UD-UCBT患儿,并且差异均有统计学意义(P<0.05)。本组成功植入并且存活超过100 d的27例患儿中,慢性GVHD(cGVHD)发生率51.8%(14/27)。本组接受allo-HSCT患儿的5年总生存(OS)率为(61.5±8.3)%(16/26),5年无病存活(DFS)率为(57.7±6.0)%(15/26)。本组34例患儿的移植相关死亡(TRM)率为23.5%(8/34)。其中,获得CR2者TRM率显著高于CR1者,并且差异有统计学意义(P<0.05)。导致TRM的原因主要为感染及自身免疫性溶血性贫血、淋巴细胞增殖病、严重GVHD。移植后ALL复发率为19.4%(6/31),复发与造血干细胞来源无明显相关性,移植后发生cGVHD者复发率更低。

结论

allo-HSCT是治疗儿童高危及复发ALL的有效手段,干细胞来源可以为脐血和外周血干细胞。接受allo-HSCT后,患儿5年OS率超过50%。CR2患者TRM率高于CR1者;发生cGVHD的ALL患儿复发风险较未发生cGVHD者低。建议对高危及复发ALL患者尽早进行allo-HSCT治疗。

Objective

To study of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk or relapsed childhood acute lymphoblastic leukemia (ALL) in first complete remission (CR1) or second complete remission (CR2), analyzing the outcomes and the impact factors.

Methods

A total of 34 cases of childhood ALL in high-risk or CR2 received allo-HSCT from April 2001 to May 2013 in SUN Yat-sen Memorial Hospital were selected into this study. Among them, 28 cases were B-cell ALL (B-ALL) and 6 cases were T-cell ALL (T-ALL); 26 cases were high-risk in CR1 and 3 cases were in CR2. According to the different donor for allo-HSCT, they were divided into match sibling donor-peripheral blood stem cell transplantation (MSD-PBSCT) group (n=5), unrelated donor-umbilical cord blood transplantation (UD-UCBT) group (n=11), and unrelated donor-peripheral blood stem cell transplantation (UD-PBSCT) group (n=18). Conditioning regimens for allo-HSCT included: busulphan (BU) + cyclophosphamide (CY), fludarabine (Flud)and human anti-thymocyte globulin (ATG). The study protocol was approved by the Ethical Review Board of Investigation in Human Being of SUN Yat-sen Memorial Hospital, SUN Yat-sen University. Informed consent was obtained from the parents of each participating child.

Results

After treatment by allo-HSCT, incidence rate of acute GVHD (aGVHD) was 33.3%, and the rate of Ⅲ-Ⅳ degrees aGVHD was 16.7%(5/30), the rate of chronic GVHD (cGVHD) was 51.8% (14/27) among 34 cases children with high-risk and relapsed ALL. Incidence rate of aGVHD in UD-PBSCT group was higher than those in other two groups. The rates of 5-year disease free survival (DFS) and overall survival (OS) were (57.7±6)% (15/26) and (61.5±8.3)% (16/26) respectively. A total of 8 cases children with high-risk and relapsed ALL died of transplant-related mortality (TRM), the rate of TRM was 23.5% (8/34). The rate of TRM in ALL children with CR2 were higher than those in ALL children with CR1, and there was significant difference (P<0.05). The major cause of the TRM was infection, and the other causes were autoimmune hemolytic anemia, severe GVHD and lymphoproliferative disorder. After treatment by allo-HSCT, among 34 cases children with high-risk and relapsed ALL, 6 cases relapsed, the relapse rate was 19.4% (6/31), and there were no significant correlation between recurrence and source of hematopoietic stem cell. The rate of relapsed was higher in patients without cGVHD, and none of the patients with cGVHD relapsed.

Conclusions

Allo-HSCT is considered as treatment for high-risk or relapsed childhood ALL, the 5-year OS rate exceeded 50%. The outcomes of allo-HSCT in childhood ALL in CR1 are better than those in CR2. Patients with cGVHD are manifested low relapse rate.

表1 本组34例接受allo-HSCT高危及复发ALL患儿临床特征构、接受allo-HSCT患儿的移植预处理方案、移植物抗宿主病预防方案、接受allo-HSCT后导致TRM的因素构成比[例数(%)]
Table 1 Constituent ratios of clinical features,allo-HSCT conditioning regimen, prevention scheme of GVHD, factors leading to TRM among 34 cases children with high-risk and relapsed ALL treatment by allo-HSCT [case(%)]
临床特征 构成比 TRM率 χ2 P 复发率 χ2 P
总例数 34 8(23.5)     6(17.6)    
性别     3.766 0.06   0.360 0.487
  25(73.5) 8(32.0)     5(20.0)    
  9(26.5) 0 (0.0)     1(11.1)    
年龄(岁)     0.384 0.417   0.551 0.571
  <10 18(52.9) 5(27.8)     4(22.2)    
  ≥10 16(47.1) 3(11.5)          
ALL分型     2.242 0.171   1.234 0.281
  T-ALL 6(17.6) 0 (0.0)     2(33.3)    
  B-ALL 28(82.4) 8(28.6)     4(14.3)    
CR     5.988 0.022   0.427 0.416
  CR1 21(61.8) 2(9.5)     3(14.3)    
  CR2 13(38.2) 6(46.2)     3(23.1)    
干细胞来源     4.948 0.084   2.312 0.325
  MSD-PBSCT 5(14.7) 0 (0.0)     2(40.0)    
  UD-UCBT 11(32.4) 5(45.5)     2(18.2)    
  UD-PBSCT 18(52.9) 3(16.7)          
移植的预处理方案     1.520 0.290   0.782 0.512
  BU+CY 29(85.3) 7(24.1)     4(13.8)    
  TBI+CY 5(14.7) 1(20.0)     2(40.0)    
GVHD预防方案     0.098 0.565   0.054 0.584
  CsA+MTX+ATG 24(70.6) 6(25.0)     4(16.7)    
  CsA+MTX+ATG+MMF 10(29.4) 2(20.0)     2(20.0)    
aGVHDa     1.103 0.500   0.877 0.500
  0 24(70.6) 6(25.0)     6(25.0)    
  Ⅰ~Ⅱ 5(14.7) 1(20.0)     0 (0.0)    
  Ⅲ~Ⅳ 5(14.7) 1(20.0)     0 (0.0)    
cGVHD     2.967 0.227   6.608 0.037
  13(48.2) 0 (0.0)     5(38.5)    
  局限性 7(25.9) 0 (0.0)     0 (0.0)    
  广泛性 7(25.9) 1(14.3)     0 (0.0)    
移植日期     0.991 0.279   0.012 0.649
  2007年前 12(35.3) 4 (8.3)     2(16.7)    
  2007年后 22(64.7) 4(18.2)     4(18.2)    
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