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

Ann Hematol. 2025 May;104(5):2683-2691. doi: 10.1007/s00277-024-06174-0. Epub 2025 Feb 20.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Fever of Unknown Origin* / blood
  • Fever of Unknown Origin* / diagnosis
  • Fever of Unknown Origin* / etiology
  • Fever of Unknown Origin* / mortality
  • Humans
  • Lymphohistiocytosis, Hemophagocytic* / blood
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / etiology
  • Lymphohistiocytosis, Hemophagocytic* / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Young Adult