单倍型异基因造血干细胞移植后发生巨细胞病毒感染的临床分析

目的 探讨单倍型异基因造血干细胞移植后发生巨细胞病毒(CMV)感染的临床特点及治疗.方法 对北京军区总医院血液科2011年1月-2013年1月采用单倍型异基因造血干细胞移植治疗的50例患者的临床资料进行回顾性研究,供者接受粒细胞集落刺激因子动员,采用骨髓加外周血干细胞联合移植,预处理方案以改良BUCY方案为主,移植后监测CMV-DNA,分析CMV感染的特点并探讨其治疗方法.结果 全部患者中男32例,女18例,年龄5-45岁,平均年龄23.8岁,其中共12例发生CMV血症,发生率为24％,首次检出CMV-DNA中位时间是移植后50天(36-72),CMV定量范围为2.4×103-6.2×106拷贝/mL,其中6例为CMV相关性出血性膀胱炎,2例为CMV相关性间质性肺炎,抗CMV治疗后全部患者CMV-DNA转阴.结论 单倍型异基因造血干细胞移植后巨细胞病毒感染发生率高,更昔洛韦、膦甲酸钠抗病毒治疗疗效可靠、不良反应少.     

EB病毒与人疱疹病毒6型感染在药疹发生中的作用

目的 本研究主要就人疱疹病毒6型(HHV-6)与EB病毒(EBV)感染在药疹产生过程中的作用展开分析,以此来为药疹患者的临床治疗提供参考.方法 选择我院2012年12月--2013年12月所收治的62例药疹患者作为观察组,另选148例健康献血人员作为对照组,采用巢式PCR对HHV6 DNA进行检测、采用PCR-Southern对EBV DNA进行检测、采用ELISA法对EBV VCA-IgM进行检测,并对其检测结果进行比较.结果 两组患者的EBV DNA、HHV6 DNA、EBV VCA-IgM阳性率存在明显差异,具有统计学意义(P＜0.05).结论 绝大部分药疹患者存在EBV感染的情况,且EBV感染与HHV6感染之间存在相互激活的作用,在药疹诊断过程中具有较高的临床应用价值,可以将其作为药疹的临床诊断指标之一.     

中国人疱疹病毒6型（HHV—6）的分离与鉴定

４例婴儿玫瑰疹病人外周血淋巴细胞与脐血淋巴细胞共培养，３例病人标本见有细胞病，其中１株病毒经多次传代和冻存后，仍能产生ＣＰＥ。该病毒株感染细胞的超薄切片在电镜下可见疱疹病毒性颗粒，感染细胞涂片与抗ＨＨＶ－６单抗产生明显荧光，用该病毒株制备的单抗与ＨＨＶ－６ Ｚ２９株荧光试验呈阳性，表明分离的病毒为ＨＨＶ－６。     

人疱疹病毒6型感染与淋巴瘤关系的初步研究

目的:研究人疱疹病毒6型(HHV-6)感染与淋巴瘤的关系。方法:用间接免疫荧光法及PCR,分别检测淋巴瘤患者和对照组患者血清中抗HHV-6 IgG及外周血单个核细胞(PBMC)中HHV-6 DNA序列。用免疫组化染色法,检测淋巴瘤患者淋巴结组织标本中HHV-6抗原。结果:淋巴瘤患者血清抗HHV-6抗体的阳性率为95.5％,几何平均滴度为1:123,PBMC中HHV-6 DNA的检出率为59.1％,均明显高于对照组(P<0.05)。免疫组化染色检测的5例淋巴瘤患者淋巴结组织标本中,4例HHV-6抗原阳性。结论:HHV-6感染可能与淋巴瘤的发病有关。     

人疱疹病毒6型感染与白血病关系的初步研究

白血病是来源于造血系统的一种恶性肿瘤，好发于儿童和青少年，其病因和发病机制尚不完全清楚，但病毒病因学较受重视。人疱疹病毒6型(HHV-6)是1986年发现的疱疹病毒科中的一个新成员。研究发现，HHV-6的感染与淋巴瘤的发生有一定关系，在白血病患者中具有较高的感染率。为了探讨HHV-6感染与白血病的关系，我们采用间接免疫荧光试验(IFA)和PCR，分别检测了白血病患者血清抗HHV-6 IgG和外周血单个核细胞(PBMC)中HHV-6 DNA的序列。     

人疱疹病毒6型感染和儿科临床疾病

人疱疹病毒6型(HHV-6)是在1986年由Salahuddin SZ从艾滋病人和淋巴细胞增生性疾患病人的末梢血单核细胞中分离到的。以后根据这种新发现病毒的病毒学特征，归类于疱疹病毒，称疱疹病毒6型。1988年日本科学家YarrlanishiK证实HHV-6是幼儿急疹的病原，并且HHV-6在原发感染后潜伏于人体，当人体免疫低下时可以再活化。本文简述了HHV-6的病毒学特征、感染的发病机理，概述了幼儿、儿童感染HHV-6的临床方面的研究进展。     

最瓣发现—人类疱疹病毒—6型为移植患者并发感染的重要病原体

本文主要介绍了人类疱疹病毒－６型在移植患者中发生感染的流行病学、临床表现、以及该病毒致病的免疫学基础、临床及控制措施。     

造血干细胞移植与自身免疫病

自身免疫与免疫耐受是当今免疫学研究的中心课题。随着免疫应答,免疫耐受机理被逐步揭示,自身免疫病的治疗越来越受到研究者及临床医生的关注。近年的研究表明造血干细胞的异常是导致自身免疫疾病的发生的根本原因,其中很多自身免疫病已在基因水平找到了相应的缺陷。本文拟从动物实验及临床治疗两方面对用造血干细胞移植治疗自身免疫病的研究与应用作一综述。     

造血干细胞移植治疗地中海贫血

背景：造血干细胞移植是目前根治地中海贫血的最佳方法,造血干细胞移植包括骨髓移植、脐血移植、宫内造血干细胞移植、外周血造血干细胞移植。 目的：利用SCI数据库文献检索和深度分析功能,对造血干细胞移植的研究文献进行多层次探讨分析。 方法：以“造血干细胞(hematopoietic stem cell or HSC);移植(transplantation);地中海贫血(thalassaemia or thalassemia);β型地中海贫血(beta thalassaemia or beta thalassemia or β thalassaemia or β thalassemia)”为关键词,检索SCI数据库2002-01/2011-12的相关文献,并将分析结果及资料导出,以文字和图表的形式进行统计和计量分析,描述其分布特征。纳入标准：检索与造血干细胞移植治疗地中海贫血相关的文献。文献类型包括：①研究原著。②会议摘要。③综述。④会议文章。⑤快报。⑥编辑素材。⑦勘误。⑧章节。⑨新闻。排除标准：①与文章目的无关的文献。②大于10年较陈旧的文献。③未发表的文章。 结果与结论：SCI数据库2002/2011共检索到8 981篇造血干细胞移植相关的文献,研究原著以4 922篇位居首位,其中有7篇可以确定为经典文献,文献数量在2002/2011呈总体上升趋势,Blood《血液》杂志发表文献量最多, 1 515篇,占全部文献的16.87%。通过文献计量学方法对来源于SCI数据库关于造血干细胞移植的文献进行分析,可为了解该领域的现状、趋势和研究者进一步确定热点难点提供有价值的参考。     

鼻咽癌组织中人疱疹病毒6型感染及其临床意义

目的　探讨人疱疹病毒６ 型（ＨＨＶ６） 与鼻咽癌（ＮＰＣ） 发病的关系。方法　采用聚合酶链反应（ＰＣＲ） 和原位杂交同时检测正常鼻咽组织和ＮＰＣ 癌前鼻咽组织以及ＮＰＣ 组织中ＨＨＶ６ 和ＥＢＶＤＮＡ 的存在情况。采用免疫组化检测３６ 例ＮＰＣ 组织的ＥＢＶＬＭＰ１ 蛋白表达。结果　在４２ 例ＮＰＣ组织、２１ 例鼻咽癌前病变组织中,经ＰＣＲ检出ＨＨＶ６ ＤＮＡ,阳性率分别为３０－９％ （１３ 例） 和４－７ ％（１ 例） 。ＥＢＶＤＮＡ为９５－２％ （４０ 例） 和６６－６ ％ （１４ 例）。２７ 例正常鼻咽组织未检出ＨＨＶ６ ＤＮＡ,ＥＢＶＤＮＡ为２５－９％ （７ 例）。经ＩＳＨ,仅在１３ 例ＰＣＲＨＨＶ６ ＤＮＡ阳性的ＮＰＣ组织中检出１１ 例阳性,３６ 例ＮＰＣ组织、１０ 例鼻咽癌前病变组织ＩＳＨＥＢＶＤＮＡ 阳性。ＮＰＣ组织的ＥＢＶＬＭＰ１ 蛋白阳性率为４７－２ ％（１７３６）。结论　鼻咽癌组织中存在ＨＨＶ６ 感染,提示ＨＨＶ６ 感染与ＮＰＣ有关。ＨＨＶ６ 感染与ＥＢ病毒ＬＭＰ１ 蛋白表达上调呈正相关,提示在ＮＰＣ 的发生中ＨＨＶ６ 可能直接参与和（ 或） 通过上调ＥＢＶＬＭＰ１ 的表达而起一定作用     

Letermovir prophylaxis for cytomegalovirus reactivation in children who underwent hematopoietic stem cell transplantation: A single-institute experience in Taiwan

From January 2019 to May 2021, 11 children underwent allogeneic stem cell transplantation at our institute. Four of them received letermovir for cytomegalovirus prophylaxis. Three children, none of whom received prophylaxis, experienced cytomegalovirus reactivation. Letermovir is a promising medication for use in cytomegalovirus prophylaxis in children. Further studies are warranted.     

人疱疹病毒6型感染与口腔鳞癌关系的初步研究

目的研究人疱疹病毒6型(HHV-6)感染与口腔鳞癌的关系。方法用间接免疫荧光试验及聚合酶链反应,分别检测口腔鳞癌和对照组患者血清中抗HHV-6 IgG及外周血单个核细胞中HHV-6 DNA序列;用免疫组化染色法检测口腔鳞癌组织标本中HHV-6抗原。结果16例口腔鳞癌患者和16例其他口腔疾病患者血清中抗HHV-6 IgG的阳性数分别为16例和12例,几何平均滴度分别为1:118和1:64,差异有显著意义(P<0.05)。上述两组患者HHV-6 DNA的检出数分别为10例和2例(P<0.05)。其中12例口腔鳞癌组织标本经免疫组化染色检测,9例(9/12)HHV-6抗原阳性,而8例对应癌旁组织中,阳性者仅有2例(2/8),两者间差异有显著意义(P<0.05)。结论HHV-6可能是口腔鳞癌发生的诱因,在肿瘤发生发展中起一定作用。     

Elevated granzyme M-expressing lymphocytes during cytomegalovirus latency and reactivation after allogeneic stem cell transplantation

Human cytomegalovirus (HCMV) reactivation can cause serious complications in allogeneic stem cell transplantation (SCT) patients. HCMV is controlled by cytotoxic lymphocytes that release antiviral granzymes. Recently, we have demonstrated that granzyme M (GrM) inhibits HCMV replication in vitro, however the physiological role of GrM and its cellular distribution during HCMV infection remains unknown. Here, we examined GrM expression in lymphocyte populations during HCMV infection. The percentage of GrM-expressing effector-memory CD4⁺ T-cells was higher in HCMV latently-infected healthy individuals compared to that of uninfected individuals. SCT recipients had higher percentages of GrM-expressing CD4⁺ T, CD8⁺ T, γδT, and NKT cells. Despite lower total T-cell numbers, HCMV reactivation in SCT patients specifically associated with higher percentages of GrM-expressing CD4⁺ (total and central-memory) T-cells. GrM was elevated in plasma during HCMV reactivation, pointing to extracellular perforin-independent functions of GrM. We conclude that GrM may be important in regulating HCMV latency and reactivation in SCT patients.     

Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation

Strategies to enhance post-transplant immune reconstitution without aggravating graft-vs-host disease (GVHD) can improve the outcome of allogeneic hematopoietic stem cell transplantation. Recent preclinical studies demonstrated that the use of T cell depleted allografts supplemented with committed progenitor cells (vs stem cells only) allows enhanced immune reconstitution of specific hematopoietic lineages including myeloid, B, T, and natural killer lineages in the absence of GVHD. This novel adoptive therapy resulted in significantly improved resistance to microbial pathogens and could, in some cases, even mediate tumor immunity. Clinical protocols using adoptive transfer of committed hematopoietic progenitor cells are currently being evaluated.     

Cytomegalovirus infection according to cell source after hematopoietic cell transplantation in pediatric patients

Purpose

This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type.

Materials and Methods

We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009.

Results

In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2×10⁵ leukocytes vs. RD 7/2×10⁵ leukocytes vs. UD 19/2×10⁵ leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia.

Conclusion

This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients.     

造血干细胞移植后出血性膀胱炎的相关因素分析

目的观察造血干细胞移植后出血性膀胱炎的发病情况,探讨其发病危险因素和防治策略。方法回顾分析2006年1月～2009年12月期间88例因恶性血液病行造血干细胞移植患者的临床资料,治疗过程中均进行常规的出血性膀胱炎和移植物抗宿主病预防,分析移植后出血性膀胱炎发生的特点及相关因素。结果共14例患者发生移植后出血性膀胱炎(15.9%),其中5例人类白细胞抗原配型全相合,12例伴有其他部位移植物抗宿主病表现,发生巨细胞病毒感染阳性6人,EB病毒阳性5人。结论在采取充分的预防措施后,出血性膀胱炎仍有发生,而受者CMV感染是造血干细胞移后发生出血性膀胱炎的重要危险因素,而与其他各项因素均无显著相关性。     

Human herpesvirus 7-associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation

A 9-year-old boy who received allogeneic stem cell transplantation began to vomit from day 10 after transplantation. In addition to vomiting, the patient had a fever (from day 26) and severe headache (from day 34). His cerebrospinal fluid (CSF) (day 41) demonstrated pleocytosis with an absence of leukemic cells. Although the patient's symptoms were resolved with further supportive care, abrupt onset of bilateral decreased vision occurred at day 54. He was diagnosed with bilateral optic neuritis, due to the presence of disc edema and redness. Concomitant with the occurrence of aseptic meningitis, the human herpesvirus 7 (HHV-7) antibody titer increased significantly in this patient. Although neither HHV-6 nor cytomegalovirus (CMV) DNA was detected in CSF collected at day 41, HHV-7 DNA was detected in the sample. Viral DNA was not detected in CSF collected at day 93.     

Comparison of six different specimen types for Epstein-Barr viral load quantification in peripheral blood of pediatric patients after heart transplantation or after allogeneic hematopoietic stem cell transplantation

Background

Epstein-Barr Virus (EBV) a gamma-herpes virus is associated with a spectrum of lymphoid and epithelial malignancies including posttransplant lymphoproliferative disorders (PTLD). EBV-load measurement has been shown to be important for the monitoring of these patients. However, in contrast to the viral quantification of human immunodeficiency virus or human hepatitis C virus, the EBV-load measurement has not been completely standardized as yet.

Objectives

In this study, we compared the EBV DNA levels in whole blood (WB), plasma, peripheral mononuclear cells (PBMC) and B-cells (BC) in children and adolescents after heart transplantations (HTx) and allogeneic hematopoietic stem cell transplantations (HSCT).

Study design

In a period of 2 years (from May 2007 to May 2009) we collected 547 samples of 96 cardiac transplant recipients and 248 samples of 37 patients who underwent HSCT. For EBV DNA quantification we used a duplex real-time PCR (ABI Prism 7500, Applied Biosystems). Additionally, EBV-load of PBMC and BC were normalized with respect to endogenous cell DNA.

Results

In both patient populations we found no significant difference of test sensitivity for the EBV detection. In PBMC as well as BC, there was a high correlation between the analysis of cells with and without normalization in both populations. Spearman's correlation coefficient ρ between PBMC without and PBMC with normalization was ρ = 0.98 (P < 0.0001) in patients after HTx and ρ = 0.99 (P < 0.0001) in patients after HSCT. Correlation between BC with and without normalization was ρ = 0.98 (P < 0.0001) in patients after HTx and ρ = 0.995 (P < 0.0001) in patients after HSCT. When comparing the different blood compartments for EBV quantification in both populations, the strongest correlations were found between the EBV DNA levels in WB and PBMC (HTx: ρ = 0.93, P < 0.0001; HSCT: ρ = 0.81, P < 0.0001) followed by PBMC and BC (HTx: ρ = 0.87, P < 0.0001; HSCT: ρ = 0.81, P < 0.0001) as well as WB and BC (HTx: ρ = 0.86, P < 0.0001; HSCT: ρ = 0.75, P < 0.0001). In contrast, the correlation coefficients between plasma and the other blood compartments (WB as well as PBMC or BC) were lower.Six patients developed seven episodes of PTLD (five patients after HTx and one after renal transplantation). Analyzing the different blood compartments, we found that a threshold of WB ≥ 20,000 EBV-copies/ml and plasma ≥ 1000 EBV-copies/ml had the highest sensitivities and specificities (WB: sensitivity 100%, specificity 87% and plasma: sensitivity 88%, specificity 98%).

Conclusion

Normalization towards an endogenous control does not seem to be necessary for EBV quantification in peripheral blood. The analysis of whole blood correlates well with B-cells and PBMC. Routine screening of EBV DNA in whole blood appeared to be a useful tool supplemented by EBV-load measurement in plasma to discriminate chronic high EBV-load carrier without risk for PTLD from those who are at risk for PTLD. Values in whole blood higher than 20,000 EBV-copies/ml WB and plasma values higher than 1000 EBV-copies/ml plasma indicated PTLD in our series.     

不同预处理移植后树突状细胞早期重建及与移植物中CD34+细胞相关性分析

目的：比较不同预处理异基因造血干细胞移植（allo-HSCT）后早期树突状细胞（DCs）亚群重建情况，以及移植物中CD34^＋细胞是否影响移植后早期DCs亚群重建。方法：采用三色流式细胞仪动态检测不同预处理移植后早期外周血树突状细胞亚群DC1、DC2水平。结果：移植后早期清髓性移植患者体内DCs亚群数量非常低，常规移植组移植后14天与半相合移植组相比，DC1、DC2均无统计学意义（P〉0．05）。非清髓性移植组（NST）DC1、DC2高于清髓性移植组，两者相比具有统计学意义（P〈0．05）。在30天和60天，所有组DC1、DC2略有波动，但是幅度不大。以输入的CD34^＋细胞数平均分为三组，三组患者DC1、DC2移植后14、30和60天均无统计学意义（P〉0．05）。结论：NST后患者早期DCs重建较清髓性干细胞移植患者早，而常规移植和半相合移植早期DCs重建较慢，二者无差别。移植物中的CD34^＋细胞不影响移植后早期DCs亚群重建。