sCD25 as an independent adverse prognostic factor in adult patients with HLH: results of a multicenter retrospective study

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal hyperinflammatory syndrome caused by an inborn or acquired error of immunity. In adults, the underlying immunodeficiency generally arises alongside severe infections, malignancies, autoimmune diseases, and immunosuppressive treatment. To analyze risk factors and outcome in adults, we conducted a multicenter retrospective study. A total of 62 adult (age ≥18 years) patients met at least one of the following inclusion criteria: (1) ≥5 of 8 HLH-2004 criteria, (2) HScore ≥ 200 plus 4 HLH-2004 criteria, or (3) mutation compatible with an HLH diagnosis. Most patients (65%) were male, and the median age at diagnosis was 53.5 years (range, 19-81 years). All patients were assigned to 4 etiologic subgroups based on their most likely HLH trigger. The survival probability of the 4 etiologic subgroups differed significantly (P = .004, log-rank test), with patients with an underlying malignancy having the worst clinical outcome (1-year survival probability of 21%). The parameters older age, malignant trigger, elevated serum levels of aspartate transferase, creatinine, international normalized ratio, lactate dehydrogenase, sCD25, and a low albumin level and platelet count at treatment initiation were significantly (P < .1) associated with worse overall survival in the univariate Cox regression model. In multivariate analysis, sCD25 remained the only significant prognostic factor (P = .005). Our results suggest that sCD25 could be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions.

Figure 1.

CONSORT diagram of patient inclusion. The search-related ICD-10 codes and time spans, numbers, and reasons for exclusions, and the total of included patients per hospital is shown.

Figure 2.

sCD25 and ferritin levels by outcome. The 4 etiologic subgroups are depicted by different colors. ∗Overlap of 3 patients (etiologies: 2 × infection, 1 × idiopathic) with sCD25 levels of 7501 U/mL and ferritin levels of 40 001 μg/L.

Figure 3.

Kaplan-Meier curves by HLH etiology. The survival probability among the 4 etiologic subgroups differed significantly (P = .004, log-rank).