Trained Immunity from Mycobacterium spp. exposure (BCG vaccination and environmental) may have an impact on the incidence of early childhood leukemia

Preventive variables for childhood leukemia incidence (LI) remain unknown. Past assertions that childhood vaccinations, especially BCG, may be potentially protective have remained disputed for over five decades because of the lack of a unifying framework to explain variable outcomes in different studies. An examination of the early childhood LI for 2020 in European Region countries with supposedly similar underlying confounders but differential childhood vaccination coverage displays negative covariation with prevailing Mycobacterium spp. exposure in BCG-vaccinated children. The childhood LI in 0-4-year-old populations with >90% childhood BCG vaccination coverage is found to be strongly but negatively correlated with prevailing tuberculin immunoreactivity [ r( 24): -0.7868, p-value: < 0.0001]. No such correlation existed for the LI in 0-4-year-old populations without BCG vaccinations, though weak associations are hinted at by the available data for MCV2, PCV3, and DTP3 vaccinations. We hypothesize that early childhood BCG vaccination priming and subsequent trained immunity augmentation by natural boosting from Mycobacterium spp. exposure play a preventive and protective role in childhood LI. The non-consideration of prevailing trained immunity could have been a cause behind the conflicting outcomes in past studies. Exploratory studies, preferably performed in high-burden countries and controlling for the trained- immunity correlate and other potential confounders, would be warranted in order to establish a role for BCG vaccination and early-life immune training (or lack thereof) in childhood LI and help put the current controversy to rest.

Automated summary

The preventive variables for childhood leukemia incidence are still unknown. Previous assertions about the potential protective effect of childhood vaccinations, particularly BCG, have been disputed due to inconsistent results in different studies. A recent examination of childhood leukemia incidence in European countries with similar confounders but varying BCG vaccination coverage has shown a negative correlation with Mycobacterium spp. exposure in BCG-vaccinated children. This suggests that early childhood BCG vaccination and subsequent trained immunity from exposure to Mycobacterium spp. may play a role in preventing and protecting against childhood leukemia.