Provisional Prognostic Score for Hemophagocytic Lymphohistiocytosis

Background

Hemophagocytic Lymphohistiocytosis (HLH) is a severe and potentially life-threatening syndrome characterized by uncontrolled activation of lymphocytes and macrophages, leading to excessive cytokine production, hyperinflammation, and tissue damage. HLH can be broadly classified into two forms: primary (familial) HLH, which is an autosomal recessive disorder often associated with genetic mutations affecting cytotoxic function, and secondary (acquired) HLH, which is triggered by infections, malignancies, autoimmune diseases, or other underlying conditions. HLH outcomes vary considerably. We conducted this study to develop a provisional HLH prognostic score (HLHPS).

Methods

We used our HLH real-world database, which contains retrospective data on 255 cases. Such data included demographics such as sex, age, and race. It also included blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 255 cases, only 219 had complete survival and outcomes data, which is the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios.

Results

The median OS of the cohort was 24 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: Age>50 (9 vs. 60 months; p=0.003), underlying malignant etiology (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 devised using these variables to identify different levels of risk. Each variable was assigned 1 point when present for a maximum possible score of 5. In this exploratory cohort, low risk was assigned a score of 0-1, intermediate risk a score of 2, and high risk a score of 3-5. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of NR, 22, and 1.8 months, respectively (p<0.0001).

Conclusion

This HLHPS is a promising new tool for risk stratification in patients with HLH. However, it still requires prospective validation.

No relevant conflicts of interest to declare.