Effect of HLA-DPB1 locus match on clinical outcomes of unrelated donor hematopoietic stem cell transplantation: a Meta-analysis
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摘要:
目的 系统评价HLA-DPB1位点不相合对非血缘供者造血干细胞移植结局的影响。 方法 检索1995年1月至2016年12月PubMed数据库、Embase数据库、国际骨髓移植中心登记处数据库(CIBMTR)、考克兰临床对照中心登记处数据库、考克兰相关文献资料数据库、中国生物医学文献数据库(CBM)、中国知网(CNKI)数据库等国内外数据库, 收集关于HLA-DPB1位点不相合对非血缘供者造血干细胞移植临床结局影响的国内外文献。采用Review Manager 5.3软件分析存活率, 植入失败发生率、移植物抗宿主病(GVHD)发生率、复发率及移植相关病死率等不良事件发生率, 并做漏斗图评估发表偏倚。 结果 纳入19篇文献, 共26 634例患者。Meta分析结果表明, 与HLA-DPB1相合组比较, HLA-DPB1不相合组受者的无病存活率较低、在非T细胞去除的移植中受者的总存活率降低, HLA-DPB1不相合组受者重症GVHD的发生率及移植相关病死率较高, 且2个位点不相合较1个位点不相合受者移植相关病死率更高。 结论 HLA-DPB1位点对非血缘供者造血干细胞移植的存活率及不良事件发生率具有明显的影响, 在选择非血缘供者时应考虑到HLA-DPB1位点的相合情况。 Abstract:Objective To systematically evaluate the effect of HLA-DPB1 mismatch on the clinical outcomes of unrelated donor hematopoietic stem cell transplantation. Methods Relevant studies analyzing the effect of HLA-DPB1 mismatch upon the clinical outcomes of unrelated donor hematopoietic stem cell transplantation published from January 1995 to December 2016 were retrieved from the PubMed, Embase, Center of International Bone Marrow Transplant Registration, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Chinese BioMedical Literature Database and China National Knowledge Infrastructure database. The survival rate, the incidence of implantation failure, graft-versus-host disease (GVHD), recurrence rate, transplantation-related mortality rate and other adverse events were analyzed by Review Manager 5.3 software. Funnel plot was utilized to assess the publication bias. Results A total of 19 literatures consisting of 26 634 patients were retrieved. Meta-analysis demonstrated that compared with the recipients in the HLA-DPB1 match group, those in the HLA-DPB1 mismatch group had lower disease-free survival rate and overall survival rate in non-T cell-depleted transplantation. In the HLA-DPB1 mismatch group, the incidence of severe GVHD and transplantation-related mortality(TRM) rate were higher. And the TRM rate of two loci mismatch was more evident than that of one locus mismatch. Conclusions HLA-DPB1 locus exerts significant effect on the survival rate and incidence of adverse events after unrelated donor hematopoietic stem cell transplantation. The status of HLA-DPB1 match should be considered when selecting the unrelated donors. -
表 1 纳入19篇文献的基本情况
Table 1. Characteristics of 19 included studies
研究作者 年份 国家或组织 HLA相合/不相合(n/n) 研究设计 患者年龄(岁) 疾病 细胞来源 随访时间 Gagne K, et al[5] 2015 法国 168/998 COS 6~67 Hem mal Unr BM, PB 2.5年 Askar M, et al[6] 2014 美国 41/186 RRCT 7~70 Hem mal Unr BM, PB 100 d Burt C, et al[7] 2014 英国 13/117 PRCT 19~660 AL, MDS Unr TCD, PB 3年 Bettens F, et al[8] 2012 瑞士 212/34 RRCT 1~70 Hem Dis Unr BM, PB, CB 5年 Fleischhauer K, et al[9] 2012 IHWG 1 719/6 820 RRCT 0.4~75.0 Hem Dis Unr BM, PB 12年 Crocchiolo R, et al[10] 2009 意大利 41/580 PRCT 19~560 Hem mal Unr BM, PB 2年 Shaw BE, et al[11] 2010 英国 89/229 PRCT 2~67 Leukemia Unr BM, PB 9年 Kawase T, et al[12] 2009 日本 1 584/3 059 Prosp cohort study 19~650 Hem mal Unr TCD BM 4年 Shaw BE, et al [13] 2007 IHWG 3 205/5 801 RRCT 1~70 Hem Dis Unr BM, PB 18年 Ludajic K, et al[14] 2008 葡萄牙 22/139 RRCT 18~630 Hem Dis Unr BM, PB 11年 Fleischhauer K, et al[15] 2006 意大利 45/27 COS 1.5~37.0 Thalassemia Unr BM 5年 Shaw BE, et al[16] 2006 英国 71/352 COS 1~65 Hem Dis Unr BM, PB 5年 Zino E, et al[17] 2004 意大利、英国 63/55 COS -0 Hem mal Unr BM 3年 Schaffer M, et al[18] 2003 瑞典 23/81 COS 0~54 Hem Dis Unr BM, PB 4年 Shaw BE, et al[19] 2003 英国 41/102 COS 1~57 Hem Dis Unr TCD 3年 Loiseau P, et al[20] 2002 法国 24/33 COS 4~50 Hem Dis Unr BM 5年 Petersdorf EW, et al[1] 2001 美国 49/156 COS 6~54 CML Unr BM 10年 Varney MD, et al[21] 1999 澳大利亚 25/67 COS 成人及儿童 - Unr BM 1年 Sasazuki T, et al[22] 1998 日本 118/245 COS 1~50 Hem Dis Unr BM 4年 PRCT为前瞻性随机对照实验; RRCT为回顾性对照研究; Prosp cohort study为前瞻性队列研究; COS为临床观察研究(设立对照组); IHWG为国际组织配型工作组; CML为慢性粒细胞白血病; Hem Dis为血液病; AL为急性白血病; MDS为骨髓增生异常综合征; Leukemia为白血病; Hem mal为血液恶性疾病; Thalassemia为地中海贫血; Unr为非血缘供者; BM为骨髓来源; PB为外周血来源; CB为脐带血; TCD为T细胞去除; -代表研究中未具体提及或难以提取 表 2 HLA-DPB1相合组和HLA-DPB1不相合组受者移植不良事件发生率的Meta分析结果
Table 2. Meta analysis results of incidence of transplant related adverse events of recipients in HLA-DPB1 matched and mismatched groups
不良事件 文献数量(个) 不相合(n是/n总) 相合(n是/n总) I2 OR(95%CI) 数值(%) P值 数值 P值 aGVHD 10 2 690/4 511 827/1 778 26 0.20 1.73(1.55~1.94) < 0.00001 Ⅲ度及以上aGVHD 10 1 716/6 170 449/1 957 0 0.78 1.31(1.16~1.48) < 0.0001 cGVHD 3 158/424 46/155 80 00.007 1.27(0.50~3.23) 0.620 植入失败 1 5/27 2/45 - - 04.89(0.88~27.24) 0.070 复发 8 2 640/12 335 1 066/3 776 0 0.46 0.68(0.62~0.74) 0 < 0.00001 TRM 5 4 646/9 422 804/2 143 55 0.07 1.39(1.26~1.54) 0 < 0.0001 -为未提供数据 表 3 HLA-DPB1的1个位点不相合和2个位点不相合受者移植相关不良事件发生率的Meta分析结果
Table 3. Meta analysis results of incidence of transplant related adverse events of recipients in HLA-DPB1 1 site and 2 sites mismatched groups
不良事件 文献数量(个) 2个位点不相合(n是/n总) 1个位点不相合(n是/n总) I2 OR(95%CI) 数值(%) P值 数值 P值 aGVHD 4 1 061/1 904 1 469/2 690 62 0.05 0.98(0.54, 1.76) 0.94 复发 3 520/2 639 1 136/5 220 0 0.73 0.87(0.77, 0.98) 0.02 TRM 2 42/114 44/181 0 0.39 1.74(1.04, 2.90) 0.04 -
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