Clinical Significance of Serum High-Density Lipoprotein Cholesterol and Its Dynamic Change in Patients with Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

Background: The lipid profile in serum is frequently dysregulated in lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). We aimed to explore the clinical significance of serum lipoprotein cholesterol in lymphoma-associated HLH.

Methods: Patients with lymphoma-associated HLH were included. Serum levels of baseline low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were collected. Serum levels of LDL-c and HDL-c after treatment (first test after treatment, time interval ≥ 14 days) were also collected.

Results: A total of 169 lymphoma-associated HLH were included. T/NK-cell lymphomas (n=88, 52.1%) account for over half of cases. Low HDL-c (< 1.03 mmol/L) was observed in 161 (95.3%) patients and low LDL-c (< 2.6 mmol/L) was presented in 145 (85.8%) patients. The best cutoff of 0.50 mmol/L for HDL-c was determined to predict the 60-day survival. Patients with HDL-c ≥ 0.50 mmol/L showed a significantly higher 60-day survival rate than patients with HDL-c <0.50 mmol/L (70.9% vs 42.2%, p < 0.001.). Patients with HDL-c ≥ 0.50 mmol/L also showed longer overall survival (OS) (median OS: 346 days vs 34 days, p < 0.001). LDL-c showed no significant impacts on 60-day survival and OS. Dynamic data of HDL-c were available in 69.2% (117) of the patients. The median interval between the two tests was 18 (IQR: 15-25) days. The level of HDL-c after treatment increased in 80.3% (94/117) of the patients. The ratio of post-treatment HDL-c/baseline HDL-c was calculated and the median number was 1.67 (IQR: 1.05-2.48). The ratio was significantly lower in the patients with T/NK-cell malignancies than those with B-cell lymphomas (median 1.40 versus 1.97, p < 0.001). A ratio of 0.78 was determined as the best cutoff to predict the 60-day survival. Patients with a ratio<0.78 had significantly reduced 60-day survival (42.4% vs 76.6%, P=0.0035, Figure 1A) and OS (median 36 days vs 407 days, P=0.0001, Figure 1B). Then we divided these patients with available data into two groups based on baseline HDL-c and the ratio of post-treatment HDL-c/baseline HDL-c: Group 1 included patients with baseline HDL-c ≥ 0.5 mmol/L and Ratio ≥ 0.78, while others were classified as Group 2. Patients in Group 2 had significantly reduced 60-day survival (57.5% vs 87.6%, P=0.0003, Figure 1C) and OS (median 107 days vs not reached, P=0.0001, Figure 1D) than Group 1.

Conclusion: Our study demonstrated serum HDL-c and its dynamic Change were robust and clinically feasible markers for predicting the outcomes of patients with lymphoma-associated HLH.