Clinical significance of high-density lipoprotein cholesterol and its dynamic change in patients with lymphoma-associated hemophagocytic lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder characterized by uncontrolled inflammation. In adults, lymphoma is the most common underlying cause. The lipid profile is frequently dysregulated in lymphoma-associated HLH (LA-HLH), and the clinical significance remains to be determined. Objectives: This study aimed to evaluate the prognostic value of baseline lipid profiles and the dynamic changes in high-density lipoprotein cholesterol (HDL-c) in adult patients with LA-HLH. Design: A multicenter, retrospective cohort study. Methods: We analyzed 277 adult patients with LA-HLH from 27 medical centers (2015–2023). Baseline lipid levels and post-treatment HDL-c levels were measured. The optimal prognostic cutoff was determined using X-tile software. Survival analysis was performed using Kaplan–Meier and Cox regression methods. Results: Low HDL-c (<1.03 mmol/L) was observed in 93.9% (260/277) patients at diagnosis. A baseline HDL-c <0.48 mmol/L was independently associated with reduced overall survival (OS; hazard ratio, HR = 1.51, 95% confidence interval, CI: 1.10–2.09, p = 0.012) and 60-day survival (HR = 1.66, 95% CI: 1.10–2.49, p = 0.015). The post-treatment/baseline HDL-c ratio was significantly lower in patients with T/NK-cell malignancies than in those with B-cell non-Hodgkin lymphoma. A lower ratio (<1.71) was significantly associated with reduced survival. Patients with both low baseline HDL-c (<0.48 mmol/L) and low ratio (<1.71) constituted a high-risk group with the worst outcomes (60-day survival: 46.7% vs 81.8%, p = 0.004; median OS: 52 days vs not reached, p < 0.001). Conclusion: HDL-c and its dynamic changes are clinically feasible markers for predicting outcomes in patients with LA-HLH.