Clinical outcomes of hemophagocytic lymphohistiocytosis in patients with HIV-related lymphomas: A multicentre observational study.

Abstract

7071 Background: Secondary Hemophagocytic Lymphohistiocytosis (HLH) is a rare and potentially fatal inflammatory disorder triggered by infections, malignancies, autoimmune diseases or drug reactions. A very limited body of evidence is available regarding HLH in people living with HIV (PLWH). The aim of this report is to evaluate the frequency, clinical characteristics and outcomes of HLH in a multicentre cohort of patients with HIV-related lymphomas (HRL). Methods: We retrospectively reviewed prospectively collected data of HRL patients treated at the National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London (2013- 2024) and at the Department of Infectious Diseases at St. Joseph Hospital Berlin-Tempelhof, Germany (2020-2024). The diagnosis of HLH was based on both the HLH-2004 diagnostic criteria and the H-Score Saint Antoine. Statistical analyses were performed using IBM SPSS software. Results: We enrolled 253 patients in this study (17.4% female at birth; median age = 48.6 years, range 21.3 – 82.9). Median CD4 count was 206 cells /µL (range, 3-1.610) with 124 patients (49.2%) having a CD4 cell count <200/µL. Mean HIV viral load (VL) was 182.458 cop/mL (range, 0-26.000 .000), with 140 (55.3%) being undetectable at the time of lymphoma diagnosis. 206 (81.4%) had advanced stage disease, III (14.4%) or IV (67%). Median follow-up was 31 months and the 5-year overall survival was 51.3%. At the time of lymphoma diagnosis, 35 patients (13.5%) were diagnosed with HLH with an H-Score ≥169 points and/or ≥ 5/8 HLH criteria with a median age of 45.7 years (range 22.8-64.2), whereas 24 patients (9.5%) had an H-Score ≥ 200 points. HLH was present in 25% of patients with Primary Effusion Lymphoma, followed by 24.2% in Burkitt Lymphoma, 18.7% in Hodgkin´s Lymphoma, 9.5% in Plasmablastic Lymphoma, and 6.6% in Diffuse-large-B-cell Lymphoma. HLH patients were more likely to be diagnosed with HIV and lymphoma simultaneously ( p=0.001 ), less likely to have a suppressed HIV-VL (31.4% vs 61 %; p < 0.01 ) and had a lower median CD4 count (102 vs. 239 cells/µL; p < 0.01 ). A significant correlation was identified between a lower CD4 count and a higher H-Score in the bivariate analysis. Patients with HLH demonstrated a significantly poorer outcome with 1-, 2-, and 5-year overall survival of 41.2%, 32.4% and 11.8% compared to patients without HLH ( p < 0.01 ) . Conclusions: HLH is considerably more frequent in HRL in comparison to lymphomas affecting the general population. Outcome is poor and comparable to published data in HIV-negative cohorts. The acquired immune disfunction and the complex interplay of HIV and oncogenic viruses such as EBV and HHV8 in this population creates multiple potential triggers for this fatal inflammatory disorder of which the immunopathological basis is yet to be understood.