PCR Screening for CMV in Umbilical Cord Blood Stem Cells

描述（由申请人提供）： 本申请是根据RFA-HL-01-016（NHLBI）提交的 创新研究资助计划。我们建议使用高灵敏度（半） 人巨细胞病毒（HCMV）的定量PCR在现有的生物 标本采集（杜克大学UCBSC项目[N 01-HB-67138]） 脐带血干细胞（UCBSC）和相关样品（母体[供体]， UCBSC和移植受体）作为确定CMV感染性的新方法 UCBSC产品除了收集生物标本外，我们还将 使用相关的现有临床数据集提供临床相关性， 分子结果。这项工作迄今尚未进行 代表了埃默里大学和杜克大学研究人员之间的新合作。CMV 在UCBSC移植受者中是一个重要的临床问题， 长期免疫力低下 约50-80%的UCBSC 献血者有现存或既往CMV感染的血清学证据。 大约10%的献血者IgM血清学阳性， 通常不用于移植（“浪费”）。 的 这些产品的浪费在财政和人力方面都是昂贵的， 在输血的研究中，血清阴性产物可能会传播 CMV，而许多血清阳性单位没有。 因此，CMV血清学检测在 UCBSC供体设置是次优的，不能预测感染性。 的 本研究的具体目的是：1）利用已经存在的生物标本 收集作为杜克大学UCBSC计划的一部分，以检查 基于核酸的检测策略，将允许确定那些 UCBSC单位可能能够通过研究以下内容传播CMV： UCBSC供体中CMV基因组元件的存在和流行，B）CMV病毒 c）母体和UCBSC样品中存在的CMV基因组物质， 血浆或细胞部分、其状态和复制能力;以及2） 使用临床数据集分析目标1中的数据， 血清学和PCR状态与CMV传播的相关性， 感染和受体结果。预计得出的数据将 显著影响UCBSC中使用CMV血清学检测的实践， 有助于更好地理解PCR对CMV的预测价值， 这种设置，导致CMV的浪费率大幅下降 血清阳性UCBSC，并改善接受者的临床结局。

DESCRIPTION (provided by applicant): This application is submitted in response to RFA-HL-01-016, the NHLBI Innovative Research Grant Program. We propose to use highly sensitive, (semi-) quantitative PCR for human cytomegalovirus (HCMV) in an existing biological specimen collection (Duke University UCBSC Program [N01-HB-67138]) of umbilical cord blood stem cells (UCBSC) and related samples (maternal [donor], UCBSC and transplant recipients) as a novel means to determine CMV infectivity of UCBSC products. In addition to this biological specimen collection, we will use the related existing clinical data set to provide clinical relevance to the molecular results obtained. This work has not heretofore been performed and represents a new collaboration between Emory and Duke investigators. CMV is a significant clinical problem in UCBSC transplant recipients, as they are profoundly immunocompromised for a protracted period. About 50-80% of UCBSC donors have serologic evidence of extant or previous CMV infection. Approximately 10% of donors have positive IgM serology, and UCBSC products from these donors are typically not used for transplantation ("wasted"). The wastage of these products is costly both in fiscal and human terms, and based on studies in blood transfusion, seronegative products likely can transmit CMV, while many seropositive units do not. Thus, CMV serologic testing in the UCBSC donor setting is suboptimal and non-predictive of infectivity. The Specific Aims of this study are to: 1) utilize the biologic specimens already collected as part of the Duke University UCBSC Program to examine the use of a nucleic acid based testing strategy that will allow determination of those UCBSC units that might be capable of transmitting CMV by studying a) the existence and prevalence of CMV genomic elements in UCBSC donors, b) CMV viral burden in maternal and UCBSC samples, c) CMV genomic material present in the plasma or cellular fraction, its state, and replication competency; and 2) To analyze the data derived from Aim 1 with the clinical data sets to permit correlation of serologic and PCR status with transmission of CMV, degree of infection, and recipient outcome. It is expected that the data derived will significantly impact the practice of using serologic testing for CMV in UCBSC, facilitate a better understanding of the predictive value of PCR for CMV in this setting, lead to a substantial decrease in the wastage rate of CMV seropositive UCBSC, and improve clinical outcomes in recipients.