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.
| Roback, John D; Caliendo, Angela M; Newman, James L et al. (2005) Comparison of cytomegalovirus polymerase chain reaction and serology for screening umbilical cord blood components. Transfusion 45:1722-8 |
