非血缘脐血移植治疗恶性血液病发生移植物抗宿主病与移植物抗白血病效应分离的机制  

Mechanism of separation of graft-versus-host disease and graft versus leukemia in unrelated cord blood transplantation for hematological malignancies

作　　者：徐安慧 林秀秀 张旭晗 宋闿迪 孙光宇 汤宝林 孙自敏 郑昌成 Xu Anhui;Lin Xiuxiu;Zhang Xuhan;Song Kaidi;Sun Guangyu;Tang Baolin;Sun Zimin;Zheng Changcheng(Department of Hematology,First Affiliated Hospital of University of Science and Technology of China,Hefei 230001,Anhui Province,China)

机构地区：[1]中国科学技术大学附属第一医院血液科,安徽省合肥市230001

出　　处：《中国组织工程研究》2022年第13期1993-1999,共7页Chinese Journal of Tissue Engineering Research

基　　金：中央高校基本科研业务费专项资金项目(WK9110000003),项目负责人:郑昌成。

摘　　要：背景:国内外多项临床研究均表明非血缘脐血移植相对于外周血干细胞或骨髓移植,不仅具有较低的移植物抗宿主病发生率,并且疾病复发率也明显降低,具有较强的移植物抗白血病效应,是临床上分离移植物抗宿主病和移植物抗白血病效应的模型之一。非血缘脐血移植后免疫细胞如何分化,为何具有较强的移植物抗白血病效应,目前机制尚不清楚。目的:回顾性分析非血缘脐血移植患者长期临床随访资料,并探讨非血缘脐血移植后优势细胞亚群及分化、相关活化与抑制分子的表达情况,进一步探讨非血缘脐血移植后移植物抗宿主病与移植物抗白血病效应分离的机制。方法:2012-07-01/2017-06-31在中国科学技术大学附属第一医院(安徽省立医院)接受造血干细胞移植治疗的成人恶性血液病患者154例,其中非血缘脐血移植93例,同胞外周血干细胞移植61例。通过收取非血缘脐血移植和外周血干细胞移植患者的骨髓标本,重点对非血缘脐血移植患者T细胞相关免疫特征进行研究,探讨非血缘脐血移植临床移植物抗宿主病与移植物抗白血病效应的分离现象。结果与结论:①经过中位61个月(42-99个月)的长期随访,非血缘脐血移植组5年慢性移植物抗宿主病发生率、5年移植后疾病复发率明显低于同胞外周血干细胞移植组(P=0.003);整合Ⅲ-Ⅳ度移植物抗宿主病、广泛性慢性移植物抗宿主病以及疾病复发、5年无移植物抗宿主病及无疾病复发生存,非血缘脐血移植组明显高于外周血干细胞移植组(P=0.038)。②非血缘脐血移植组CD3^(+)T细胞明显高于外周血干细胞移植组(P=0.04)。非血缘脐血移植组CD3^(+)CD4^(+)T细胞亚群比例低于外周血干细胞移植组;非血缘脐血移植组CD3^(+)CD8^(+)细胞亚群比例高于外周血干细胞移植组;非血缘脐血移植组CD4^(+)CD80^(+)T细胞低于外周血干细胞移植组(P=0.089),且非血缘�BACKGROUND:Numerous clinical studies in and outside China have shown that unrelated cord blood transplantation has a lower incidence of graft-versus-host disease compared with peripheral blood stem cell or bone marrow transplantation,and the recurrence rate of the disease is also markedly reduced.It has a strong graft versus leukemia effect and is one of the models for clinically separating graft-versus-host disease and graft versus leukemia effect.How the immune cells differentiate after unrelated cord blood transplantation and why the transplant has a strong graft versus leukemia effect;the mechanism is still unclear.OBJECTIVE:To retrospectively analyze the long-term clinical follow-up data of unrelated cord blood transplantation patients,investigate dominant cell subsets and differentiation,related activation and expression of inhibitory molecules after unrelated cord blood transplantation,and further explore the mechanism of graft-versus-host disease and graft versus leukemia separation of unrelated cord blood transplantation.METHODS:From July 1,2012 to June 31,2017,154 adult patients with hematologic malignancies received hematopoietic stem cell transplantation,including 93 cases of unrelated cord blood transplantation and 61 cases of sibling peripheral blood stem cell transplantation.The immune characteristics of T cells in patients with unrelated cord blood transplantation were studied by collecting bone marrow samples from patients with unrelated cord blood transplantation and peripheral blood stem cell transplantation,and the separation of clinical graft-versus-host disease and graft versus leukemia effect in unrelated cord blood transplantation was investigated.RESULTS AND CONCLUSION:(1)After a median follow-up of 61 months(42-99 months),the 5-year prevalence of chronic graft-versus-host disease and five year-relapse in unrelated cord blood transplantation group were significantly lower than those in peripheral blood stem cell transplantation group(P=0.003).Integration of III-IV graft-versus-host diseas

关 键 词：脐血 外周血干细胞 移植 移植物抗宿主病 移植物抗白血病效应 T细胞 免疫功能 

分 类 号：R457[医药卫生—治疗学] R394.2[医药卫生—临床医学]