e19033 Background: Lymphocyte-depleted Hodgkin's lymphoma (LDHL) is an aggressive, rare form of Hodgkin’s lymphoma (HL). The LDHL reticular subtype (LDHL-R) is characterized by a scant invasion of lymphocytes without an increase in collagen fibers by fibroblasts. Patient demographics and clinical features of LDHL-R are poorly understood, causing it to frequently be misdiagnosed as other variants of HL. At diagnosis, patients have often already progressed to late disease staging. The demographic and socioeconomic factors of patients diagnosed with LDHL-R within the National Cancer Database (NCDB) were analyzed to better understand its epidemiology. Methods: A retrospective cohort analysis was performed using data from the 2004-2020 NCDB of the 51 cases of LDHL-R (ICD-O-3 9655). Demographic and socioeconomic factors such as age, sex, race, Hispanic status, treatment facility type, Charles-Deyo score, and 90-day mortality were examined using descriptive statistics. Diagnostic trends were quantified through regression analysis. Results: A total of 51 patients were diagnosed with Hodgkin lymphoma, lymphocyte depletion, reticular subtype within the NCDB. The most common primary site of diagnosis was within lymph nodes of multiple regions (41%). The majority of patients were males (65%), White (72%), and non-Hispanic (74%). Patients tended to have residence in metropolitan counties with populations greater than 1 million (71%) and were enrolled in academic/research programs (36%). Most of the patients were privately insured (41%) followed by those insured by Medicare (29%). A higher percentage of patients were in the top quartile of income earners (31%) than those in the second, third, or fourth quartiles. The incidence rate of diagnosis remained constant from 2004 to 2020 (R² = 0.02). The mean age of diagnosis was 51 years (SD=21, Range=14–90). Using the AJCC System, patients tended to be classified as Stage IV (41%) at diagnosis and had a Charlson-Deyo comorbidity score of 0 (71%). Primary treatment methods involved chemotherapy (84%) and radiation therapy (20%). Surgical intervention was given to 14 patients, and post-surgery survival rates were 93% after 90 days. Conclusions: To the best of our knowledge, this is the first NCDB analysis of the demographic factors of patients diagnosed with LDHL-R. Consistent with previous studies about the aggressiveness of this subtype of Hodgkin’s Lymphoma, most patients received a Stage IV diagnosis. Understanding LDHL-R’s epidemiology could result in significantly earlier diagnoses and improved prognosis. Patients tended to be male, White, and non-Hispanic with a residence in metropolitan counties. To improve understanding of the impact of demographic and socioeconomic factors of the diagnosis, treatment, and survival of patients with LDHL-R, more research is recommended.