KIR配体—配体模式对无关供者造血干细胞移植预后评估的meta分析
发布时间：2019-05-16 12:54
【摘要】：背景：杀伤细胞免疫球蛋白样受体(Killer cell immunoglobulin-like receptors,KIR)表达在NK细胞(Natural killer cell)表面并与人类白细胞抗原(Human leukocyte antigen, HLA) Ⅰ类分子相互作用传递抑制或者活化信号,从而影响NK细胞的功能。目前认为,当细胞表面不表达或者低表达(譬如感染或肿瘤)与KIR相应的HLA-I类分子时,NK细胞被激活,攻击并溶解受到感染的细胞或瘤细胞。而供受者之间KIR与其配体的匹配模式以及匹配程度与造血干细胞移植主要并发症及预后相关,其中配体-配体模式被定义为供者包含的KIR配体中有患者所缺失的KIR配体存在。相关文献显示,KIR配体-配体模式与无关供者造血干细胞移植(Hematopoietic stem cell transplantation, HSCT)的预后密切相关。本文通过检索1994-2012年期间的相关文献进行meta分析为无关供者的选择及HSCT风险预判提供参考。方法：检索pub med、medline、Embase以及The Cochrane Library几个数据库中1994-2012年在线的相关文献,以"Killer cell immunoglobulin-like receptors/KIR" "HSCT/hematopoietic stem cell transplantation"为关键字进行检索。将检索到的文献根据纳入标准逐一进行排除后获得纳入文献。对纳入文献进行数据提取,需要提取的数据包括：病例数、患者平均年龄、HLA相合程度、干细胞来源、病种、疾病分期以及是否使用体外去除T细胞(T cell depleted,TCD)或抗胸腺细胞球蛋白(Anti-thymocyte globulin,ATG)等；观察的效应指标：5年总生存率(Overall survival,OS),Ⅱ-Ⅳ级急性移植物抗宿主病(Acute graft-versus-host disease,acute GVHD)发生率,复发率(Relapse),移植相关死亡率(Transplant-related mortality,TRM)。提取数据后应用Revman 5.0对所获得的数据进行分析。结果：通过关键词"KIR/killer immunoglobulin like receptor"和"HSCT/hematopoieticstem cell transplantation"共检索到197篇文献,经过筛选后纳入7篇文献,包括3845例患者。我们meta分析的结果显示：供受者KIR配体匹配组较错配组在OS上更具优势(OR：odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04);然而,两组在2-4度GVHD发生率(OR=0.94,CI=0.71-1.24,P=0.64),5年复发率(OR=1.05,CI= 0.75-1.47,P=0.77)以及TRM上并没有显著的差异(OR=0.61,CI=0.15-2.51,P=0.50)。结论：通过对KIR的配体-配体模式在无关供者HSCT的OS、Ⅱ-Ⅳ级GVHD、TRM以及复发率进行meta分析,我们发现无关供者造血干细胞移植供受者KIR配体匹配对患者的总生存更加有利,而在2-4度急性GVHD、复发及移植相关死亡率等方面则没有显著的差异,但是这种结果可能会受到HLA相合程度,T细胞去除以及疾病本身特性的影响。
[Abstract]:Background: killer cell immunoglobulin-like receptor (Killer cell immunoglobulin-like receptors,KIR is expressed on the surface of NK cell (Natural killer cell) and interacts with human leukocyte antigen (Human leukocyte antigen, HLA) class I molecules to transmit inhibitory or activation signals. Thus affecting the function of NK cells. At present, it is believed that when HLA-I molecules corresponding to KIR are not expressed or underexpressed on the surface of cells (such as infection or tumor), NK cells are activated, attacked and dissolved into infected cells or tumor cells. The matching pattern and degree of matching between donors and recipients of KIR and its ligands are related to the main complications and prognosis of hematopoietic stem cell transplantation, in which ligand-ligand pattern is defined as the presence of missing KIR ligands in KIR ligands contained in donors. The related literature shows that the KIR ligand-ligand model is closely related to the prognosis of unrelated donor hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation, HSCT). In this paper, meta analysis is carried out by searching the relevant literature from 1994 to 2012 to provide a reference for the selection of unrelated donors and the prediction of HSCT risk. Methods: the relevant literatures of pub med,medline,Embase and The Cochrane Library from 1994 to 2012 were searched and searched with the keyword "Killer cell immunoglobulin-like receptors/KIR" and "HSCT/hematopoietic stem cell transplantation". The searched literature is excluded one by one according to the inclusion criteria and then included in the literature. The data to be extracted from the included literature include the number of cases, the average age of the patient, the degree of HLA coincidence, the origin of stem cells, the disease type, the stage of the disease, and whether to remove T cell (T cell depleted, in vitro. TCD) or antithymoglobulin (Anti-thymocyte globulin,ATG), etc. The 5-year overall survival rate (Overall survival,OS), the incidence of grade II-IV acute graft-versus-host disease (Acute graft-versus-host disease,acute GVHD) and the recurrence rate of (Relapse), transplantation-related mortality (Transplant-related mortality,TRM) were observed. After extracting the data, Revman 5.0 was used to analyze the obtained data. Results: a total of 197 articles were searched by the keywords "KIR/killer immunoglobulin like receptor" and "HSCT/hematopoieticstem cell transplantation". After screening, 7 articles, including 3845 patients, were included. The results of our meta analysis showed that the donor and recipient KIR ligand matching group had more advantages on OS than the mismatched group (OR:odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04). However, there was no significant difference in the incidence of 2: 4 degree GVHD (OR=0.94,CI=0.71-1.24,P=0.64), 5-year recurrence rate (OR=1.05,CI= 0.75 卤1.47, P = 0.77) and TRM between the two groups (OR=0.61,). CI=0.15-2.51,P=0.50) Conclusion: by meta analysis of OS, grade II-IV GVHD,TRM and recurrence rate of KIR ligand-ligand pattern in unrelated donor HSCT, we found that donor and recipient KIR ligand matching of unrelated donor hematopoietic stem cell transplantation was more beneficial to the total survival of patients. However, there was no significant difference in the recurrence of acute GVHD, and the mortality associated with transplantation, but this result may be affected by the degree of HLA coincidence, T cell removal and the characteristics of the disease itself.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R457.7
本文编号：2478293
[Abstract]:Background: killer cell immunoglobulin-like receptor (Killer cell immunoglobulin-like receptors,KIR is expressed on the surface of NK cell (Natural killer cell) and interacts with human leukocyte antigen (Human leukocyte antigen, HLA) class I molecules to transmit inhibitory or activation signals. Thus affecting the function of NK cells. At present, it is believed that when HLA-I molecules corresponding to KIR are not expressed or underexpressed on the surface of cells (such as infection or tumor), NK cells are activated, attacked and dissolved into infected cells or tumor cells. The matching pattern and degree of matching between donors and recipients of KIR and its ligands are related to the main complications and prognosis of hematopoietic stem cell transplantation, in which ligand-ligand pattern is defined as the presence of missing KIR ligands in KIR ligands contained in donors. The related literature shows that the KIR ligand-ligand model is closely related to the prognosis of unrelated donor hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation, HSCT). In this paper, meta analysis is carried out by searching the relevant literature from 1994 to 2012 to provide a reference for the selection of unrelated donors and the prediction of HSCT risk. Methods: the relevant literatures of pub med,medline,Embase and The Cochrane Library from 1994 to 2012 were searched and searched with the keyword "Killer cell immunoglobulin-like receptors/KIR" and "HSCT/hematopoietic stem cell transplantation". The searched literature is excluded one by one according to the inclusion criteria and then included in the literature. The data to be extracted from the included literature include the number of cases, the average age of the patient, the degree of HLA coincidence, the origin of stem cells, the disease type, the stage of the disease, and whether to remove T cell (T cell depleted, in vitro. TCD) or antithymoglobulin (Anti-thymocyte globulin,ATG), etc. The 5-year overall survival rate (Overall survival,OS), the incidence of grade II-IV acute graft-versus-host disease (Acute graft-versus-host disease,acute GVHD) and the recurrence rate of (Relapse), transplantation-related mortality (Transplant-related mortality,TRM) were observed. After extracting the data, Revman 5.0 was used to analyze the obtained data. Results: a total of 197 articles were searched by the keywords "KIR/killer immunoglobulin like receptor" and "HSCT/hematopoieticstem cell transplantation". After screening, 7 articles, including 3845 patients, were included. The results of our meta analysis showed that the donor and recipient KIR ligand matching group had more advantages on OS than the mismatched group (OR:odds ratio=1.93,95% CI:95% confidence interval=1.03-3.61,P=0.04). However, there was no significant difference in the incidence of 2: 4 degree GVHD (OR=0.94,CI=0.71-1.24,P=0.64), 5-year recurrence rate (OR=1.05,CI= 0.75 卤1.47, P = 0.77) and TRM between the two groups (OR=0.61,). CI=0.15-2.51,P=0.50) Conclusion: by meta analysis of OS, grade II-IV GVHD,TRM and recurrence rate of KIR ligand-ligand pattern in unrelated donor HSCT, we found that donor and recipient KIR ligand matching of unrelated donor hematopoietic stem cell transplantation was more beneficial to the total survival of patients. However, there was no significant difference in the recurrence of acute GVHD, and the mortality associated with transplantation, but this result may be affected by the degree of HLA coincidence, T cell removal and the characteristics of the disease itself.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R457.7
【共引文献】
相关博士学位论文 前1条
1 姜波;K562-4-1BBL-MICA工程细胞构建及其联合IL-21对NK细胞体外扩增的研究[D];吉林大学;2014年
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