骨髓移植患者EBV、CMV及BKV感染的动态监测及临床意义

发布时间：2018-01-10 00:10

本文关键词：骨髓移植患者EBV、CMV及BKV感染的动态监测及临床意义　出处：《大连医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:通过实时荧光定量PCR(Real-time quantitative PCR,RT-PCR)检测造血干细胞移植前后患者血液或尿液中EB病毒(Epstein-Barr virus,EBV)、巨细胞病毒(Cytomegalovirus,CMV)、BK病毒(BK virus,BKV)的基因拷贝数,监测移植前后患者的EBV、CMV及BKV的感染情况,对患者临床特征及其感染情况进行回顾性分析研究。方法:收集并分析自2014年7月至2016年11月期间进行自体及异基因造血干细胞移植(Hematopoietic stem cell transplantation,HSCT)患者病毒血清学抗体情况及其临床资料。从移植前3周开始应用RT-PCR每周1次检测患者外周血EBV-DNA、CMV-DNA及尿液BKV-DNA基因拷贝数。采用SPSS 19.0进行统计分析,P0.05具有统计学意义。结果:1.共83例患者纳入研究。男女比例接近1:1;成人与儿童比例约3:1;白血病与非白血病患者比例约为1:1。2.血清学抗体检测示所有患者EBV-Ig G均为阳性,CMV-Ig G阳性率为90.4%,异基因移植的61例患者中,1例为D-/R+(D/R:Donor/Receptor,供者/受者;-/+:Ig G阴性/Ig G阳性),7例为D+/R-,53例为D+/R+;其中D-/R+患者移植后CMV激活,D+/R-患者移植后CMV感染率(57.1%)较D+/R+(26.4%)略高(P=0.095)。3.EBV激活率为33.7%,异基因移植显著较自体移植患者EBV感染率高(P=0.004),抗胸腺球蛋白(Antithymocyte globulin,ATG)应用患者较未应用患者高(P=0.000)。移植后患者中2例发生移植后淋巴细胞增殖性疾病(Posttransplantation Lymphoproliferative disorders,PTLD)(2/83,2.4%)。EBV感染可显著降低移植后患者的总体生存率(P=0.0469)。4.CMV的感染率为22.9%,CMV病毒血症患者中CMV相关疾病的发生率为36.8%(7/19),其中5例呼吸系统疾病及2例胃肠道系统疾病。自体移植患者移植后无CMV感染发生,异基因移植患者CMV感染率为31.1%;ATG应用患者CMV感染率显著高于未应用ATG的患者(P=0.003),其中发生CMV疾病的患者均有ATG的应用;供者为男性的患者CMV感染率较供者为女性的患者高(P=0.049)。5.BKV的感染率为47.0%(39/83),其中有24例(61.5%,24/39)发生出血性膀胱炎(hemorrhagic cystitis,HC),其病毒尿症持续的中位时间为118天;而未发生HC的患者病毒尿症持续的中位时间为88天。急性淋巴细胞白血病(Acute lymphocytic leukemia,ALL)患者HC的发生率明显低于急性髓细胞白血病(Acute myelocytic leukemia,AML)患者(P=0.026);异基因移植患者BKV感染率较自体移植患者高(P=0.002),亲缘单倍型移植患者HC的发生率显著高于全相合移植患者(P=0.006);骨髓及外周血干细胞来源的患者HC发生率高于仅外周血干细胞来源的患者(P=0.002);应用ATG的患者BKV感染率(P=0.01)和HC发生率(P=0.002)均显著较未应用ATG的患者高。结论:1.EBV、CMV及BKV是造血干细胞移植后常见的病毒感染病原体,多种因素均可对移植后患者病毒感染或体内潜伏病毒活化状况产生影响。2.移植类型及ATG的应用对移植后患者EBV、CMV及BKV的感染情况均有显著影响;干细胞来源对病毒的感染率无显著影响,但可以显著影响EB及BK病毒相关疾病的发生;HLA相合度及白血病类型对BKV感染率无显著影响,但可显著影响BKV相关性HC的发生。3.常规ELISA法检测血清学病毒抗体不能及时准确地反应患者当下病毒的实际感染情况,但对移植后患者的病毒的激活情况有一定的预测作用;RT-PCR对病毒DNA的检测较为灵敏,能对移植患者血液及尿液常见病毒DNA进行实时动态监测。4.抗病毒药物的积极预防及抢先应用可明显减低移植后患者病毒感染率及病毒相关疾病的发生。
[Abstract]:Objective: through real-time fluorescence quantitative PCR (Real-time quantitative PCR, RT-PCR) detection of hematopoietic stem cell transplantation patients before and after blood or urine EB virus (Epstein-Barr virus, EBV), cytomegalovirus (Cytomegalovirus, CMV), BK virus (BK virus BKV) gene copy number of EBV patients before and after transplantation monitoring, infection CMV and BKV, the clinical characteristics and infection were analyzed retrospectively. Methods: collected and analyzed from July 2014 to November 2016 during the period of autologous and allogeneic hematopoietic stem cell transplantation (Hematopoietic stem cell transplantation, HSCT) in patients with viral serology and clinical data from 3 weeks before transplantation. RT-PCR was applied weekly 1 detection of peripheral blood in patients with EBV-DNA, CMV-DNA and urine BKV-DNA gene copy number. SPSS 19 was used for statistical analysis, with statistical significance. Results: a total of 83 1. P0.05 Patients were enrolled. The proportion of male and female adults and children close to 1:1; the ratio of about 3:1; the proportion of patients with leukemia and non leukemia is about 1:1.2. serological test showed that all patients with EBV-Ig G were positive, the positive rate of CMV-Ig G was 90.4%, 61 cases of allogeneic transplantation patients, 1 cases were D- /R+ (D/R:Donor/Receptor, donor recipient: Ig / + /; G negative /Ig G positive), 7 cases were D+/R-, 53 cases of D+/R+ patients with D-/R+ after transplantation; the activation of CMV, D+/R- after transplantation, CMV infection rate (57.1%) than D+/R+ (26.4%) is slightly higher (P=0.095).3.EBV activation rate was 33.7%, allogeneic transplantation was significantly higher than that of EBV patients with autologous transplantation of high infection rate (P=0.004), anti thymocyte globulin (Antithymocyte, globulin, ATG) than those who did not use applications with high (P=0.000). After transplantation in patients with 2 cases of post transplant lymphoproliferative disease (Posttransplantation Lymphoproliferative disorders PTLD (2/83,2.) 4%).EBV infection can significantly reduce the total survival rate of patients after transplantation (P=0.0469).4.CMV infection rate was 22.9%, CMV viremia in patients with CMV related disease incidence rate was 36.8% (7/19), including 5 cases of respiratory diseases and 2 cases of gastrointestinal system disease. CMV infection occurred in patients after autologous transplantation CMV, the infection rate of patients with allogeneic transplantation was 31.1%; the infection rate of ATG patients was significantly higher than that of non CMV patients using ATG (P=0.003), application of which occurred CMV disease patients had ATG; donor for rate is for male patients with CMV infection for female patients with high.5.BKV (P=0.049) infection rate 47% (39/83), of which 24 cases (61.5%, 24/39) had hemorrhagic cystitis (hemorrhagic cystitis, HC), the viruria median duration of 118 days; but did not occur in patients with HC viruria median duration of 88 days. Acute lymphoblastic leukemia Disease (Acute lymphocytic leukemia, ALL) in patients with HC significantly lower incidence of acute myeloid leukemia (Acute myelocytic, leukemia, AML) patients (P=0.026); BKV patients with allogeneic transplantation with autologous transplantation in patients with high infection rate (P=0.002), the incidence of haploidentical transplantation patients with HC was significantly higher than that of matched transplant patients (P=0.006); bone marrow and peripheral blood stem cells from patients with the incidence of HC was higher than that of peripheral blood stem cells from patients (P=0.002); application of ATG (P=0.01) in patients with BKV infection rate and the incidence rate of HC (P=0.002) were significantly less ATG patients. Conclusion: 1.EBV, CMV and BKV are the most common pathogens the virus infection after hematopoietic stem cell transplantation, transplantation of multiple factors can patients after viral infection or latent virus affects the application of.2. type and ATG transplantation on patients with EBV after transplantation of CMV and BKV activation, the infection had Significant effect; source of stem cells for the virus infection rate had no significant effect, but can significantly affect EB and BK virus related diseases; HLA matched degree and type of leukemia on BKV infection rate has no significant effect, but can significantly affect the occurrence of actual infection.3. conventional ELISA serological detection of virus antibody can not be timely and accurate response current the correlation between BKV virus in patients with HC, but the activation of virus in patients after transplantation have a predictive effect; detection of virus DNA RT-PCR is more sensitive, active prevention of transplant patients in blood and urine of common virus DNA for real-time dynamic monitoring of.4. and preemptive antiviral drugs can significantly reduce the rate of application and the related virus patients with viral infection after transplantation.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R457.7

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