异基因造血干细胞移植后T细胞再生及其临床意义

异基因造血干细胞移植包括已广泛开展的异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）异基因外周血干细胞移植（Ａｌｌｏ－ＰＢＳＣＴ）以及脐带血血干细胞移植（ＣＢＴ）。它是治愈血液系统恶性肿瘤和其它多种疾病的有效手段。移植后在造血系统恢复的同时,免疫系统也在经历一个重建过程,Ｔ细胞再生通过胸腺依赖途径和胸腺非依赖途径。成人由于胸腺功能退化,Ｔ细胞再生更多是靠成熟Ｔ细胞的外周扩增和胸腺外分化,造成Ｔ细胞库多样性受限,     

异基因造血干细胞移植后T细胞免疫重建与临床预后相关性研究进展

异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)已经成为当前治疗血液系统恶性肿瘤的先进手段之一,作为唯一可以治愈血液系统恶性肿瘤的治疗方式,患者接受移植后迅速而良好的免疫重建往往预示着较好的临床预后,其中T细胞的恢复情况对临...     

异基因造血干细胞移植后早期和成就T细胞亚群的恢复

对２１例异基因造血干细胞移植病人移植后３个月内外周血Ｔ细胞ＣＤ３＾－ＣＤ５＾＋和ＣＤ３＾＋ＣＤ５＾＋亚群的百分比进行了测定。ＣＤ３＾－ＣＤ５＾＋细胞作为早期胸腺细胞的标志,在移植后３个月内均低于正常对照,ＣＤ３＾＋ＣＤ＾＋细胞作为成熟Ｔ细胞的标志,在移植后２－３个月开始恢复,说明移植后早期（３个月内）Ｔ细胞数量的恢复主要依靠成就Ｔ细胞的扩增。ＣＤ３＾＋ＣＤ５＾＋细胞在发生急性移植物抗宿主病的病人中     

异基因造血干细胞移植后树突状细胞重建动力学

树突状细胞（DC）作为体内最重要的抗原呈递细胞,其移植后重建在移植合并症,如移植物抗宿主病（GVHD）、感染以及复发中发挥着重要作用,成为移植免疫领域研究的热点问题之一。本文就异基因造血干细胞移植（allo-HSCT）后DC重建规律及其与移植合并症的关系,以及影响DC重建过程的正负性因素作一综述。     

造血干细胞移植后免疫功能重建及其检测

造血干细胞移植 (HSCT)是指受者接受各种来源的造血干细胞达到造血重建和免疫重建 ,是根治某些血液系统恶性疾病、实体瘤、基因缺陷病及自身免疫性疾病的一种重要手段。对肿瘤患者进行HSCT时 ,致死量的预处理化疗不仅能相对彻底杀灭受者体内肿瘤细胞 ,也有利于移植后重建的免疫功能发挥移植物抗肿瘤效应 (GVT )及进一步清除微小残留病 (MRD) ,而达到治愈的目的。移植后造血功能重建常被看作移植成功的标志。但免疫功能重建时间较长 ,且有较大的个体差异 ,而容易被忽视。因此对HSCT后的免疫功能重建进行定期监测 ,并采取相应的干预性…     

异基因造血干细胞移植后细胞免疫重建与真菌感染的相关性

目的探讨血液恶性肿瘤患者异基因造血干细胞移植(allo-HSCT)后CD4+T细胞免疫重建及其与侵袭性真菌感染(IFI)的关系。方法选取2010年2月—2014年10月滨州医学院附属医院行allo-HSCT的血液恶性肿瘤患者47例,以同期体检健康者40名作为对照组。分别于移植后1、2、3个月采用流式细胞术检测患者移植后免疫细胞亚群数,采用酶联免疫吸附试验(ELISA)检测细胞因子浓度。观察患者移植后IFI发生情况,及其与CD4+T细胞免疫重建的相关性。结果移植后CD4+T细胞及其免疫细胞亚群数随时间递增,但移植后3个月免疫细胞亚群数仍低于对照组;与对照组比较,移植后白细胞介素(IL)-6和IL-10水平升高,转化生长因子(TGF)-β水平降低;IFI发生率为19.15%(9/47)。多因素Logistic回归分析结果显示,IFI可能与辅助性T细胞(Th)17的细胞数有关,而与Th1、Th2、调节性T细胞细胞数以及IL-6、IL-10、TGF-β和干扰素(IFN)-γ水平无关。结论 CD4+T细胞免疫重建延迟、Th17细胞数明显减少可能与allo-HSCT后IFI的发生有关。     

全相合异基因造血干细胞移植后免疫重建的研究

目的探讨人类白细胞抗原(HLA)全相合异基因造血干细胞移植(allo-HSCT)后免疫重建的规律。方法选择42例2009至2013年在瑞金医院血液科骨髓移植病区接受allo-HSCT患者,采用速率散射比浊法检测预处理前和移植后1、3、6、12及24个月的血清免疫球蛋白IgG、IgA、IgM及IgE水平,流式细胞术(FCM)检测预处理前,移植日,移植后14、21 d和1、3、6、12、18及24个月的T淋巴细胞(CD3+、CD3+CD4+、CD3+CD8+)、B细胞(CD19+)及自然杀伤(NK)细胞(CD56+CD16+),总结移植后免疫球蛋白及各淋巴细胞亚群的恢复情况并对影响免疫重建的因素进行探讨。结果 CD3+及CD3+CD8+T细胞移植后14 d开始恢复正常,CD3+CD4+T细胞恢复缓慢,在术后2年内低于或接近正常水平。CD56+CD16+细胞移植后恢复较快,21 d左右开始恢复正常水平。CD19+细胞在移植后6个月左右恢复正常,免疫球蛋白IgM、IgG、IgA恢复正常的时间分别为1、3及6个月。不同性别患者移植后免疫重建无明显差异,供体来自同胞的患者免疫重建速度较非血缘移植快。发生严重感染及Ⅲ~Ⅳ移植物抗宿主病(GVHD)患者CD3+CD8+T细胞水平移植后早期明显高于未发生GVHD及感染者。发生Ⅲ~ⅣGVHD患者移植后早期CD3+细胞明显高于未发生GVHD患者,并且CD3+CD4+T细胞恢复有延迟趋势。结论 allo-HSCT后淋巴细胞亚群的免疫重建顺序依次是:CD56+CD16+,CD3+CD8+,CD19+及CD3+CD4+。HLA全相合有利于免疫重建,移植治疗中抗胸腺球蛋白的应用、移植后GVHD发生等是影响免疫重建的最重要因素。     

造血干细胞移植后免疫重建的研究进展

造血干细胞移植(HSCT)后受者的免疫功能受到严重损坏,关于移植后免疫细胞状态及重建移植后免疫功能的研究,对于防治移植后感染和肿瘤复发有重要意义。本文就HSCT后免疫重建的研究现状做一综述。     

非清髓异基因造血干细胞移植后免疫重建的初步研究

我们观察了 5例白血病患者行非清髓异基因造血干细胞移植 (NAST)后免疫重建的情况 ,现报道如下。对象和方法1　研究对象　 5例均为本院 2 0 0 0年 1 2月～ 2 0 0 1年 6月行NAST的白血病患者 ,1 0名不吸烟的健康成人作为对照组。患者的一般资料见表 1。预处理方案 :氟达拉滨 (Flud) 30mg·m-2 ·d-1 ,移植前第 9天 (- 9天 )～ - 5天或环磷酰胺 (CTX)30mg·kg-1 ·d-1 ,- 4～ - 3天 ;白消安 (BU) 2mg·kg-1 ·d-1 ,- 8～ - 5天 ;抗胸腺细胞球蛋白 (ATG) 1 0mg·kg-1 ·d-1 ,- 7～ - 4天。环孢菌素A(CsA) 2mg·kg-1 ·d-1 ,- 1天开始用…     

造血干细胞移植后骨髓造血重建中血细胞形态学变化

为了解造血干细胞后骨髓造血重建中血细胞形态学变化规律，以利病情观察及制订治疗方案，对６例采用不含全身照射（ＴＢＩ）以马法兰，阿糖胞苷，环磷酰胺（ＭＡＣ）作预处理方案进行造血干细胞移植者术后每天在常规检查，每周行骨髓细胞学检查，并进行分析，发现造血干细胞移植后１－２周骨髓极度受抑，第３周骨髓出现恢复征象，５－６周骨髓造血恢复正常，红系恢复中阳先出现中，晚幼红细胞，粒系以原粒，早幼粒先出现巨核系统最民     

IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into lethally irradiated hosts suggested that recent thymic emigrants can undergo homeostatic proliferation and acquire a memory-like phenotype. We found by BrdU pulse-chase, cell cycle, and annexin V analyses that IL-7 administration has significant proliferative and antiapoptotic effects on posttransplant peripheral T cells. We conclude that homeostatic expansion is important for T cell reconstitution after allogeneic BMT and involves both transferred mature T cells and recent thymic emigrants. Apart from its thymopoietic effects, IL-7 promotes peripheral T cell reconstitution through its selective proliferative and antiapoptotic effects on nonalloreactive and de novo-generated T cells, but has no effect on alloreactive T cells.     

Immune reconstitution after autologous hematopoietic stem cell transplantation

Autologous hematopoietic stem cell transplantation has proved to be an effective treatment for certain hematologic malignancies. However, relapse rates are high during the first year after transplantation. These relapses are attributed to the failure of high-dose chemotherapy to eradicate minimal residual malignant disease. In allogeneic hematopoietic stem cell transplantation, the higher antitumor effects observed compared with those in autologous hematopoietic stem cell transplantation are based on the immunologically mediated graft-vs-tumor effect. Therefore, a better understanding of the mechanisms involved in immune reconstitution after hematopoietic stem cell transplantation may clarify the importance of various components of the recovery of the immune system as they pertain to eradication of residual tumor, as well as uncover possible interventions directed at maximizing this effect. This review focuses on immune reconstitution after autologous hematopoietic stem cell transplantation. Autologous hematopoietic stem cell transplantation is not affected by graft-vs-host disease or immunosuppressive therapy after transplantation to control graft-vs-host disease, providing a direct insight into the mechanisms involved in immune reconstitution after engraftment.     

异基因造血干细胞移植后的长期随访

背景:近20年来中国的造血干细胞移植工作迅速发展,接受异基因造血干细胞移植后得到治愈的患者越来越多,但关于患者移植后长期随访情况的报道少见.目的:总结异基因造血干细胞移植后患者的长期随访情况.方法:对1995/2005在中山大学附属第三医院进行异基因造血干细胞移植的30例患者进行长期随访,总结患者的远期并发症、长期生存率、死亡原因,调查长期生存患者的生活质量.结果与结论:30例患者的慢性移植物抗宿主病发生率为67%,所有患者均出现不育,1例轻度肺纤维化,无其他远期并发症;移植后2年的无病生存率为60%,2年内未复发的患者均长期生存,生存时间最长的1例已超过14年;12例患者死亡,均发生于移植后2年内,其中5例死于复发,7例为移植相关死亡(均死于感染);长期生存的患者移植后1年时的生活质量较差,随着生存时间的延长生活质量逐渐改善,5年时的生活质量明显提高,8年时多已拥有较高的生活质量,影响生活质量的主要因素是慢性移植物抗宿主病.     

Graft failure after allogeneic hematopoietic stem cell transplantation

Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Successful transplantation depends on the formation of engrafment, in which donor cells are integrated into the recipient’s cell population.In this paper, we distinguish two different entities, graft failure (GF) and poor graft function (PGF), and review the current comprehensions of the interactions between the immune and hematopoietic compartments in these conditions. Factors associated with graft failure include histocompatibility locus antigen (HLA)-mismatched grafts, underlying disease, type of conditioning regimen and stem cell source employed, low stem cell dose, ex vivo T-cell depletion, major ABO incompatibility, female donor grafts for male recipients, disease status at transplantation.Although several approaches have been developed which aimed to prevent graft rejection, establish successful engraftment and treat graft failure, GF remains a major obstacle to the success of allo-HSCT.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) still remains to be the curative treatment option for various non-malignant and malignant hematopoietic diseases. The outcome of allo-HSCT primarily depends on the engraftment of the graft. Graft failure (GF), is a life-threatening complication which needs the preferential therapeutic manipulation. In this paper, we focused on the definitions of graft failure / poor graft function and also we reviewed the current understanding of the pathophysiology, risk factors and treatment approaches for these entities.     

Immune reconstitution: the foundation for safe living after an allogeneic hematopoietic stem cell transplantation

With increasing frequency, oncology nurses are providing long-term care to hematopoietic stem cell transplantation (HSCT) recipients in nontransplantation settings. This may be a result of more patients receiving HSCTs, recipients living longer, and recipients' desire to return to their hometowns as soon as possible. Although critical to patients' initial recovery after HSCT, immune reconstitution also must remain a priority of oncology nursing care long beyond the date of discharge from a transplantation center. As patients resume their normal lives, oncology nurses need to be diligent in assessment and education to facilitate the ultimate goal, a safe life after HSCT. This article provides concise details about the short- and long-term immunologic effects of HSCT and focuses on the long-standing threat of opportunistic infections that can persist months and years after HSCT.     

异基因造血干细胞移植后嵌合状态与白血病复发关系的研究

目的 探讨异基因造血干细胞移植（allo HSCT）后嵌合状态与白血病复发的关系。方法 回顾性分析2014年1月至2018年6月于我院行清髓性allo HSCT的成人白血病患者73例,采用短串联重复序列 聚合酶链反应（STR PCR）检测移植后+30、+60、+90天受者骨髓的供受者细胞嵌合率,分析嵌合率与复发的关系。结果 移植后+90天复发组嵌合率低于非复发组。移植后+60 d、+90 d低嵌合患者有较高的复发率（P=0.021,0.027）。多因素分析显示移植前疾病状态、+60d嵌合率、+90d嵌合率是白血病患者行allo HSCT后复发的独立危险因素。结论 Allo HSCT后嵌合状态对复发具有预测价值,+60、+90天低嵌合患者有较高的复发率。     

Nonmyeloablative allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based on a two-step approach: first, the use of immunosuppressive (but nonmyeloablative) preparative regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. Preliminary results showed that NMSCT were feasible with a relatively low transplant-related mortality (TRM), even in patients older than 65 years. In addition, strong antitumor responses were observed in several hematological malignancies as well as in some patients with renal cell carcinoma. After discussing the mechanisms and efficacy of the GVL effect as well as the rationale for NMSCT strategies, this article reviews the first results of ongoing clinical trials. Innovative modalities that may permit amplification of the GVL effect while minimizing the risk of GVHD are discussed. Because the benefits of NMSCT over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.