A potential association between congenital cytomegalovirus (cCMV) infection and hyperdiploid cases of pediatric acute lymphoblastic leukemia (ALL) was identified by researchers in a new population-based study with results reported in JAMA Network Open.
ALL is the most prevalent type of cancer in the pediatric population, and some possible risk factors have been identified in connection with it. However, most often the cause of ALL is unknown. Some studies have suggested that CMV may be a risk factor for ALL, which may appear and be detected as a congenital infection.
“As universal newborn screening for cCMV is in development, it is important to establish through replication whether CMV infection at birth is a risk factor for ALL,” the researchers performing this study wrote in their report. They set out to determine if they could identify a link between cCMV and a risk of pediatric ALL.
The study was a case-control analysis of patients of ages 0 to 14 years with ALL, who were matched at a 1:4 ratio to cancer-free control individuals without ALL. The researchers examined newborn dried blood spots for the presence of cCMV infection using quantitative polymerase chain reaction-based analyses. They then performed logistic regression analyses to determine whether cCMV infection or other variables showed associations with ALL.
The study evaluated 1189 patients with ALL and 4756 matched control individuals. Evidence of a cCMV infection was identified in 6 (0.5%) patients with ALL and in 21 (0.4%) control individuals. In a multivariable analysis, each group showed a similar odds of having cCMV infection (adjusted odds ratio, 1.30, 95% CI, 0.52-3.24).
Among individuals who tested positive for cCMV, the mean CMV viral load identified in patients with ALL was 3301.3 copies/mg of genomic DNA (SD, 6576.5), compared with a mean of 840.1 copies/mg of genomic DNA (SD, 1256.2) in the control population. However, this did not reflect a statistically significant difference (P =.10).
Details on immunophenotype were evaluable in 45.1% of patients with ALL, and on cytogenetic data in 27%. When subtype of ALL was considered, the odds ratio for detection of cCMV infection was 6.26-times (95% CI, 1.44-27.19) higher with patients having hyperdiploid ALL than with control individuals, in an unmatched analysis involving all control individuals.
“Our findings suggest a CMV-ALL association may be specific to hyperdiploid ALL, consistent with recent reports from diagnostic specimens,” the researchers explained. They highlighted a need for continued research to explore this possible association. “Future work may also consider incorporating DNA methylation to help establish a mechanistic link between cCMV and ALL,” they wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Geris JM, Schleiss MR, Hooten AJ, et al. Evaluation of the association between congenital cytomegalovirus infection and pediatric acute lymphoblastic leukemia. JAMA Netw Open. 2023;6(1):e2250219. doi:10.1001/jamanetworkopen.2022.50219