Associations between early‐life and in utero infections and cytomegalovirus‐positive acute lymphoblastic leukemia in children. Issue 5 (1st October 2022) - Gallant, Rachel E.
Abstract: Childhood infections and cytomegalovirus (CMV) are associated with pediatric acute lymphoblastic leukemia (ALL). CMV dysregulates the host immune system and alters the immune response to subsequent antigenic exposures. We suspect that this immune dysregulation contributes to increased numbers of symptomatic infections in childhood allowing for expansion of pre‐leukemic clones. We explored the association between childhood infections, maternal infections during pregnancy and CMV‐positive ALL. Using a droplet digital PCR assay, we screened diagnostic ALL bone marrow samples from the California Childhood Leukemia Study (1995‐2015) for the presence of CMV DNA identifying CMV‐positive and CMV‐negative cases. We performed a case‐only analysis (n = 524) comparing the number and types of childhood infections and maternal infections during pregnancy between CMV‐positive and CMV‐negative ALL cases using logistic regression. With increasing numbers of infections in the first 12 months of life, children were more likely to classify to the highest tertile of CMV DNA in the bone marrow at diagnosis (OR: 1.04, 95% CI: 1.01‐1.08). Specifically, those reporting cough or flu in the first 12 months were more likely to be CMV‐positive at ALL diagnosis (OR: 2.15, 95% CI: 1.06‐4.37 and OR: 2.06, 95% CI: 1.17‐3.63 respectively). Furthermore, those with a history of maternal infection during pregnancy were more likely to be CMV‐positive (OR: 2.12, 95% CI: 1.24‐3.62). We hypothesize that children with underlying immune dysregulation develop more symptomatic infections in childhood and ultimately CMV‐positive ALL; this underlying immune dysregulation may be due to early immune system alterations via CMV exposure (in utero or early infancy) proposing a potential link between CMV and ALL etiology. Abstract : What's new? Cytomegalovirus (CMV) infection early in life likely contributes to the development of childhood acute lymphoblastic leukemia (ALL), owing to CMV‐induced alterations in immune function. In the present study, the relationship between risk of childhood ALL and exposure to CMV in utero or early life was investigated among children with ALL who participated in the California Childhood Leukemia Study. Case‐only analysis shows that children exposed to maternal infections during pregnancy are more likely to have CMV‐positive ALL than CMV‐negative ALL. Children with increased numbers of infections in early life are more likely to be CMV‐positive at the time of ALL diagnosis.