Cytomegalovirus viral load in cord blood and impact of congenital infection on markers of hematopoietic progenitor cell potency

Abstract

BACKGROUND The low incidence of cytomegalovirus (CMV) infection in neonates decreases the risk of viral transmission with cord blood transplantation. Cord blood donors are screened by testing the maternal sample for total antibodies to CMV. Some cord blood banks also screen cord blood for CMV‐DNA. The aim of this study was to develop and validate a multiplex real‐time polymerase chain reaction assay to measure CMV viral load in cord blood from asymptomatic infants with congenital CMV infection and to assess the impact of CMV infection on cord blood hematopoietic progenitor cell concentrations and colony‐forming unit functionality. STUDY DESIGN AND METHODS CMV infection was evaluated in two groups of cord blood donors: 1) 30,308 neonates prospectively screened by saliva culture, including 41 positive cases (0.14%), all from mothers with total antibodies to CMV; and 2) 4712 newborns from mothers with total antibodies to CMV who were screened retrospectively by polymerase chain reaction, including 18 positive cases (0.38%). All 59 infants with CMV were asymptomatic at birth. RESULTS Among the 59 positive cases, the average CMV viral load in cord blood was 20.6 × 104 viral copies (vc)/mL; seven of 59 mothers (12%) had CMV‐DNA detected, however, with no association to their newborns' CMV viral load. Levels of colony‐forming units, CD34+/CD45+ cells, and total nucleated cells measured in a cohort of CMV‐positive cord blood samples were higher than those in the matched control group. CONCLUSION We developed and validated a multiplex real‐time polymerase chain reaction assay to detect CMV‐DNA in cord blood. In our study, maternal total antibodies to CMV or CMV‐DNA at birth were poor predictors of infection in cord blood donors. Furthermore, our results suggest that CMV congenital infection impacts CD34+/CD45+ cells and some hematopoietic progenitor cells toward higher proliferation.

Age and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B-cell precursor populations

“… 52 CMV infection acquired during pregnancy or perinatally has been associated with childhood B-ALL 52 , 53 , 54 and been shown to affect hematopoietic progenitors in cord blood. 55 , 56 CMV triggers signaling through TLR3, 57 , 58 raising the possibility that the potentially proleukemic activity observed in our study may be generated by early exposure to the virus. Although the strongest evidence for a role for CMV is reported for hyperdiploid B-ALL, we observed a similar magnitude of effect across a range of leukemia subtypes.…”

Evaluation of the Association Between Congenital Cytomegalovirus Infection and Pediatric Acute Lymphoblastic Leukemia

“…The association between cCMV and B lymphocytes are CD34 + cells, which are early hematopoietic progenitor cells in bone marrow, and the cell type in which CMV establishes latency. A study by Albano et al investigated the impact of cCMV on hematopoietic progenitor cell concentrations in cord blood and found among infants with cCMV infection, CD34 + cell populations were roughly 2.6 times greater than those of matched controls. This suggests a mechanism by which cCMV increases the risk of ALL by encouraging proliferation of cells vulnerable to transformation.…”

Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review

“…Viral infections are important causes of morbidity and mortality in patients undergoing allo-HSCT. Therefore, careful screening and testing of UCB units seems be critical to exclude the potential UCB units with viral contaminations and to reduce the risk of UCB-related virus transmission[4,5].…”