The Association Between Cytomegalovirus Infection and Increased Leukemia Incidence: A Retrospective Matched Cohort

Introduction Cytomegalovirus (CMV) is a common viral infection with high global seroprevalence that often remains dormant throughout life. While typically asymptomatic, early exposure has been linked in some studies to hematologic malignancies, including acute myelogenous leukemia (AML). Evidence suggests CMV may play both protective and contributory roles in leukemogenesis. This retrospective study evaluates the correlation between CMV infection and the incidence of leukemia in a national cohort. Methods This retrospective matched cohort study used data from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database (PearlDiver Marina, PearlDiver Technologies Inc., Colorado Springs, CO) using International Classification of Diseases (ICD)-9 and ICD-10 codes. Inclusion required at least eight years of continuous active status. Controls were matched 1:1 to CMV patients by age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were conducted using Pearson's chi-square tests, with odds ratios (ORs), relative risk (RR), and 95% confidence intervals (CIs) reported. Two-tailed p-values < 0.05 were considered significant. Results Between January 2010 and December 2019, 14,268 patients with CMV infection were matched 1:1 to 14,268 controls. The incidence of leukemia was 2.61% (373/14,268) in the CMV group and 1.56% (224/14,268) in controls (RR 1.66, 95% CI 1.41-1.94; OR 1.69, 95% CI 1.44-1.97; p < 0.001). A temporally restricted analysis isolating incident leukemia cases following CMV exposure demonstrated a statistically significant correlation between CMV infection and leukemia. Conclusion Prior CMV infection was associated with an increased risk of developing leukemia in subsequent years, supporting the need for additional studies to validate these findings and identify the underlying mechanisms of CMV-related hematologic malignancy.