Disparity Analysis of Clinical Features and Prognostic Evaluation of Hemophagocytic Lymphohistiocytosis in Pediatric and Adult Patients: A Retrospective Multicenter Study of 525 Cases in HHLWG

Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare immune disorder with rapid progression and high mortality. There have been few large cohort study comparisons of pediatric and adult HLH until now. This study was designed to explore the disparity of clinical presentations and evaluate the prognosis in pediatric and adult HLH patients. Methods: Totally, 525 newly diagnosed HLH patients were included and divided into 4 groups according to age: <6, 6–18, 18–60, and >60 years (geriatric patients). Mann-Whitney U test, Kruskal-Wallis test, χ2 test, and Bonferroni’s adjustment were used to explore the difference between age groups. Overall survival (OS) was estimated by using Kaplan-Meier method. The Cox proportional hazard model was used to analyze the univariable and multivariable association between prognostic factors and OS. Results: Geriatric patients had the lowest levels of hemoglobin, platelet, albumin, and the highest level of creatinine, while patients <6 years of age had the lowest values of fibrinogen, IgA, IgM and highest values of triglyceride. The trigger of HLH in patients <18 years of age was mainly EBV infection. However, lymphoma and non-EBV-driven infection were the more frequent drivers in patients aged 18–60 and >60 years, respectively. Geriatric patients were associated with highest mortality (58.8%), and 5-year OS was 43%. By contrast, 5-year OS of patients <6, 6–18, and 18–60 years was 86.1%, 74%, and 58.9%, respectively. Additionally, among patients with different etiologies (EBV, non-EBV-driven infection, and uncertain causes) and treatment regimens (HLH-04, HLH-94, and glucocorticoid regimen), geriatric patients showed lowest 5-year OS. Multivariate analysis revealed that creatinine and alanine aminotransferase were independent risk factors affecting the survival of patients aged 0–6 years, while albumin and IgG were independent factors affecting survival of geriatric patients. Conclusion: Our study showed a wide heterogeneity of clinical presentations, etiology distribution, prognostic factors, and survival outcomes in pediatric and adult HLH patients.