AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology?

Abstract

Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study . BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6؋ that among females and among non-Hispanic blacks, 0.4؋ that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence IntroductionBurkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) with 3 clinical variants: endemic (eBL), sporadic (sBL), and acquired immunodeficiency-associated BL (aBL). 1 These clinical variants, which are defined in part by where they occur geographically, are histologically indistinguishable 1 and their etiology is incompletely understood. 2 eBL occurs in children mostly as extranodal jaw or orbital masses in equatorial Africa and Papua New Guinea. 3 sBL occurs anywhere in the world at any age mostly with abdominal or nodal involvement. [4][5] Immunodeficiencyassociated BL is diagnosed in people with HIV, 1 among whom it is often the first indication of AIDS onset at least in the West. Risk for both eBL and sBL appears to be highest at ages 5-9 years and sBL rates are also elevated at the oldest ages. 4,6 Because BL is a rapidly growing tumor, doubling its cell mass approximately every 1-2 days, 7 the interval from trigger to diagnosis may be relatively short, so study of age-specific risk may provide etiologic information.In an assessment of age-specific risk for BL in the United States, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (1973-2005), 8 we observed 3 incidence peaks near ages 10, 40, and 70 years among males and 2 peaks near ages 10 and 70 years among females for both whites and blacks. However, the role of AIDS-related immunosuppression could not be excluded 9,10 because we were not able to separately analyze AIDS and non-AIDS BL. To address this limitation, we investigated age-specific BL incidence among persons with AIDS (PWA) in the United States Because age is a surrogate for cumulative exposure to deleterious infections a linear increase in risk for BL with age in PWA would suggest cumulative impact of deleterious infections given immunosuppression, whereas a nonlinear risk increase would suggest that age may be a surrogate for differences in the etiology or biology of BL diagnosed at different ages that occur independent of immunosuppression. 8 MethodsData...

Trends in survival of patients with Burkitt lymphoma/leukemia in the USA: an analysis of 3691 cases

“…This association seems independent of the immune status, and HIV1 patients are at high risk of BL even with relatively high CD41 count. 23 Currently nearly 20% of BL diagnoses in the United States are in HIV1 patients. 11 Even though aggressive treatments are feasible in HIV1 patients, leading to results similar to the ones seen in the HIV2 population, 24,25 it is unknown if the lack of discrepancy in outcomes is due to patient selection.…”

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

“…Interestingly, some GC-B cells also express the activation marker CD71 [27] and CD71 was identified as a non-immunoglobulin partner of BCL6 translocation, a common abnormality in NHL [28]. Finally, data by Guech-Ongey et al [29], suggested that in some AIDS-NHL cases malignant cells require functional CD4 lymphocytes to thrive. Supporting this finding, we determined a positive correlation between the frequency of the potentially malignant abnormal activated/GC-like B cells and CD4+ T cell count.…”

AIDS-related BL and CD4 count: a clue?

“…1 Rodent T-ALLs induced by a variety of genetic manipulations also exhibit frequent Notch1 mutations that render them Notch1-dependent for survival and proliferation in vitro. 1 Thus, aberrant Notch1 activation represents a key event in the multistep pathway of T-cell leukemogenesis in rodents and humans. Two articles in this issue report the unexpected finding that spontaneous or Cre-LoxP-targeted deletion of the 5Ј Notch1 promoter allows generation of leukemogenic Notch1 from "cryptic" internal promoters.…”