Clinical characteristics and prognostic factors in patients with fever of unknown origin who developed secondary haemophagocytic lymphohistiocytosis

Abstract

Background: Patients with fever of unknown origin (FUO) can sometimes be accompanied by haemophagocytic lymphohistiocytosis (HLH), a life-threatening disease. The prognostic model and specific markers for the early prognosis and the optimized treatment regimen are of considerable research interest.

Results: A total of 135 FUO/HLH patients were enrolled and classified according to the 60-day outcomes following diagnosis. 79 patients (including 5 patients lost in follow-up) enrolled from 2007 to 2015 served as the derivation cohort, and 56 patients from 2016 to 2023 served as the validation cohort. In the derivation cohort, 27 patients (27/74, 36.5%) survived within 60 days and multivariate analyses showed that age > 67 years (P = 0.003), baseline PLT < 42 × 10^9/L (P = 0.012) and LDH > 1505 U/L (P = 0.002) were associated with a higher mortality rate in HLH patients. The external validation proved the reliability of the prediction model. In derivation cohort, the median alteration of PLT (△PLT) were + 78 × 10^9/L and - 17 × 10^9/L in the survival and non-survival groups, respectively (P < 0.001). The median △LDH was - 197.5U/L in the survival group, while in the non-survival group was + 119U/L (P < 0.001).

Conclusions: Age, baseline LDH and PLT levels may predict early mortality in secondary HLH patients and identify patients in critical conditions. △LDH and △PLT levels were of high value to monitor the efficacy of therapeutic regimen and the disease progression in HLH patients.

Keywords: Autoimmune diseases; Fever of unknown origin; Hematologic malignancies; Infections; Secondary haemophagocytic lymphohistiocytosis.

Fig. 1

The alteration in laboratory findings between the baseline point and the endpoint. “△” is equal to the endpoint value minus the baseline value

Fig. 2

Survival curves by survival and non-survival groups. Kaplan-Meier analyses of 60-day OS in patients with HLH according to age (a), jaundice (b), PLT (c) and LDH (d). Abbreviations: PLT: Platelet; LDH: lactate dehydrogenase

Fig. 3

Establishment and validation of a prognostic model for HLH. (a)Calibration plots of overall survival at 60 days. Overall survival curves for derivation cohort (b) and validation cohort (c)