Nonlinear Burkitt lymphoma risk patterns with age and CD4 lymphocyte count among persons with AIDS in the United States

Abstract

Background: Trimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the U.S. general population, particularly among men. Because BL is AIDSrelated, it is not known whether trimodal incidence peaks occur independently of immunosuppression. We therefore investigated age-specific BL incidence in persons with AIDS (PWA). Methods: Crude and adjusted incidence rates, rate ratios (IRR), and 95% confidence intervals (95% CI) for BL and other non-Hodgkin lymphomas (NHLs) diagnosed during 4- 60 months following AIDS diagnosis in the United States HIV/AIDS Cancer Match study (1980-2005) were assessed by age and CD4 lymphocyte counts using Poisson regression models. Two-tailed p-values < 0.05 were considered statistically significant. Findings: We analyzed 306 incident cases (22 cases per 100,000 person-years) diagnosed among 567,865 PWA. The adjusted incidence rate ratio for BL among males was 1.6 times that among females and among non-Hispanic Blacks 0.4 times that among non-Hispanic Whites, but it was unrelated to HIV-transmission categories. The age-specific incidence rates for BL revealed at least two and perhaps three peaks during the pediatric and adult/geriatric years, whereas the incidence rates for other NHLs increased from childhood to adulthood. Compared to PWA aged 32-39 years, the adjusted incidence rate ratio (IRR) for BL was significantly elevated among PWA aged 0-19 years (2.3, 95% CI 1.2-4.4). The adjusted IRR for BL among PWA aged 20-31 years was significantly decreased (0.6, 95% CI 0.4-0.8), but the adjusted IRRs for BL among PWA aged 40-51 years, 52-59 years, and aged 60 years or older were not significantly different (1.0, 95% CI 0.8- 1.3), (0.8, 95% CI 0.4-1.4), and (1.4, 95% CI 0.7-2.7), respectively. The risk for BL among PWA with <50 CD4 lymphocytes/μL was 0.3 (95% CI=0.2-0.6) of those with ≥250 CD4 lymphocytes/μL, whereas the incidence for other NHLs rose with decreasing CD4 lymphocyte counts. Interpretation: Our findings strengthen the notion that bi/trimodal BL may occur independently of immunosuppression. The deficit of BL at low CD4 lymphocyte counts suggests that functional CD4 lymphocytes may be required for BL to develop.