Abstract 3368: Hemophagocytic lymphohistiocytosis provisional prognostic score

Abstract Background: Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by the uncontrolled activation of lymphocytes and macrophages, leading to excessive cytokine production, hyperinflammation, and tissue damage. HLH presents in two forms: primary (familial) HLH, associated with autosomal recessive genetic mutations affecting cytotoxic function, and secondary (acquired) HLH, triggered by infections, malignancies, autoimmune diseases, or other underlying conditions. Given the variability in HLH outcomes, this study aimed to develop a provisional prognostic score (HLHPS) to stratify patient risk. Methods: We analyzed data from a real-world HLH database, comprising 255 cases. Data included demographic information (sex, age, race), blood counts, comorbidities, immunohistochemical and molecular disease phenotypes, treatment types, and survival outcomes. Of these, 219 cases with complete survival data were selected for analysis. A Cox proportional-hazards model and Log-rank tests were applied to identify clinicopathologic factors significantly affecting overall survival (OS), which were then incorporated into a provisional prognostic score based on the impact of hazard ratios. Results: The median OS for the cohort was 24 months. The key prognostic factors identified were: age >50 (9 vs. 60 months; p=0.003), underlying malignancy (2 vs. 60 months; p=0.0004), splenomegaly (22 vs. NR months; p=0.02), LDH >1000 U/L (24 vs. NR months; p=0.003), and sIL2R >5000 U/ml (6 vs. NR months; p=0.03). A prognostic model was created using these variables, with each variable assigned 1 point when present, for a total score ranging from 0 to 5. Risk categories were defined as low (0-1 points), intermediate (2 points), and high (3-5 points). This prognostic score system led to our cohort's most optimal risk discriminatory model, with low, intermediate, and high risk groups having a median OS of NR, 22, and 1.8 months, respectively (p<0.0001). Conclusion: The HLHPS is a promising tool for risk stratification in HLH patients, offering a new approach to predict outcomes. However, further prospective validation is necessary to confirm its utility. Citation Format: Philip A. Haddad, Suma Chennapragada, Deepti Kantamani, S. Jashwanth Gaddam. Hemophagocytic lymphohistiocytosis provisional prognostic score [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3368.