Influence of HIV status, age and ethnicity on survival in patients with burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL): A real-world nationwide database study

Abstract Introduction: BL and DLBCL are the two most common lymphomas associated with HIV infection. Notably, clinical trials often exclude HIV-positive patients and prior retrospective studies often lacked long-term follow-up on overall survival (OS). This has limited our knowledge about the influence of HIV status on survival in BL and DLBCL. Survival outcomes can also vary significantly across ethnic groups, influenced mostly by disparities in healthcare access and socioeconomic status. Additionally, survival rates differ among age groups, which may be attributed to tolerance to intensive chemotherapy and the presence of comorbid medical conditions. Our study primarily focused on comparing OS between HIV-positive and negative patients with DLBCL and BL in the real world. We also examined OS disparities among diverse ethnicities and age groups. Method: Patients diagnosed with DLBCL and BL were identified from the Cerner Health Facts database over five years from 2013 to 2018 using ICD-9 and ICD-10 codes. Within this cohort, individuals with a positive HIV status were identified through specific ICD-9 and ICD-10 codes. Demographic characteristics including age, gender, and ethnicity were collected for all patients, and they were stratified into distinct age groups: 20 years, 20-39 years, 40-59 years, 60-79 years, and 80+ years. OS was calculated for all patients from the time of diagnosis to time of death or hospice discharge. A multivariate cox regression model was employed to adjust for confounding variables. Results: The total number of patients diagnosed with DLBCL and BL was 10,534. Of these patients, 45.3% were female. The ethnic composition included 77% Caucasian, 10.3% African American and 12.7 % from other ethnicities. Among this population, 315 patients were HIV positive. In the cohort of DLBCL patients, 8,275 were HIV negative and 185 were HIV positive. In the cohort of BL patients, 1,944 were HIV negative and 130 were HIV positive. Among patients with DLBCL, HIV positive status had more than two-fold higher mortality rate compared to their HIV negative counterparts (HR=2.1, 95% CI 1.31 to 3.36, p=0.0018). Patients with BL who were HIV positive had no difference in OS in comparison to the HIV negative group (p=0.575). African American patients with DLBCL had almost 40% increased risk of mortality compared to Caucasian patients (HR=1.39, 95% CI 1.05-1.83, p=0.017). African American patients with BL had no difference in OS compared to Caucasian patients (p=0.3). Patients aged 60-79 years were found to have 44% higher risk of mortality compared to 40-59 age group (HR=1.44, 95% CI 1.13-1.83, p=0.0033) and patients aged 80 years or above were found to have more than two-fold higher risk of mortality in the DLBCL cohort (HR=2.16, 95% CI 1.63-2.87, p0.0001). For patients with BL, those aged 20-39 had half the risk of mortality as compared to the 40-59 age group (HR= 0.50, 95% CI 0.28 - 0.87, p=0.014) whereas patients aged 80 or older had almost three times higher risk of mortality (HR = 2.87, 95% CI 1.81-4.57, p0.0001). Conclusion: HIV status can significantly influence survival outcomes in patients diagnosed with DLBCL. Early identification of HIV infection, along with the initiation of prompt antiretroviral therapy and the administration of appropriate intensive chemotherapy regimens, is crucial for optimizing treatment outcomes in this patient population. Notably, our study indicates that African American patients exhibit a higher mortality rate compared to their Caucasian counterparts with DLBCL. This could be related to disparities in access to healthcare and treatment resources across different ethnicities. Moreover, it also indicates possible lymphoma biological heterogeneity in various ethnicities. Furthermore, elderly patients demonstrate increased mortality rates likely attributed to a greater prevalence of frailty, indicating the need for innovative less intense regimens for these patients with DLBCL and BL.