Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry

Abstract

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults.

Methods: Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded.

Results: The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17-87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*10⁹/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival.

Conclusion: Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.

Keywords: Cytokine storm; HLH; Hemophagocytic lymphohistiocytosis; Inflammation; Sepsis.

Fig. 1

Kaplan–Meier plot showing overall survival for different HLH subgroups. Patients with malignancy-associated HLH had the shortest median survival time, although no statistically significant difference between the subgroups was observed (log-rank test: p =  0.077)