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. 2020 Mar 12;15(1):71.
doi: 10.1186/s13023-020-1336-6.

Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis

Jun Zhou  1 , Jing Zhou  1 , Dan-Ting Shen  1 , Hemant Goyal  2 , Zhi-Qi Wu  3 , Hua-Guo Xu  4
Affiliations

Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis

Jun Zhou et al. Orphanet J Rare Dis. .

Abstract

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical syndrome with high mortality rate. The diagnosis of HLH draws on a constellation of clinical and laboratory abnormalities including extremely high serum ferritin levels. However, no biomarker has been firmly established as a clinically useful prognostic tool in HLH patients. We aimed to perform a retrospective analysis of two independent cohorts to explore the prognostic value of discharge serum ferritin for newly diagnosed adult HLH patients who recently started treatment. The prognostic value of serum ferritin levels at discharge (will be called as post-treatment ferritin level) was initially evaluated in a "test cohort" of 161 previously untreated consecutive adult HLH patients. It was then validated in a second cohort of 68 consecutive previously untreated patients (validation cohort).

Results: Multivariate analysis revealed that significantly high post-treatment serum ferritin levels (>1050 μg/L) were associated with a higher risk of death and poor overall survival in the test cohort (hazard ratio (HR): 3.176, 95% confidence interval (CI) 1.468-6.869, P = 0.003), and the validation cohort (HR: 13.412, 95%CI 1.716-104.816, P = 0.013). At 6-month follow-up period in the test cohort, patients with a > 81% decrease in the serum ferritin level had a significantly higher probability of survival when compared with the patients with ≥14% increase in the serum ferritin level (94% vs. 31%, P < 0.001). Similar findings were observed on the analysis of the decrease in the serum ferritin level in the validation cohort.

Conclusions: These results suggest that the serum ferritin level can be used as an independent prognostic marker in the adult HLH patients.

Keywords: Adult; Ferritin; Hemophagocytic Lymphohistiocytosis; Overall survival; Prognosis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Performance of serum ferritin in different subgroups of adult HLH patients in the test cohort. a Adult HLH patients with post-treatment serum ferritin > 1050 μg/L showed significantly worse OS than those with post-treatment serum ferritin ≤1050 μg/L. b Infection-associated adult HLH patients with post-treatment serum ferritin > 1050 μg/L showed significantly worse OS than those with post-treatment serum ferritin ≤1050 μg/L. c Malignancy-associated adult HLH patients with post-treatment serum ferritin > 1050 μg/L showed significantly worse OS than those with post-treatment serum ferritin ≤1050 μg/L. (D) Overall survival, stratified according to quartiles of serum ferritin decrease
Fig. 2
Fig. 2
Performance of serum ferritin in the validation cohort. a Adult HLH patients with post-treatment serum ferritin > 1050 μg/L showed significantly worse OS than those with post-treatment serum ferritin ≤1050 μg/L. b Overall survival, stratified according to quartiles of serum ferritin decrease getting from the test cohort
Fig. 3
Fig. 3
Adult HLH outcome, stratified according to quartiles of serum ferritin decrease in the test cohort. a Comparisons of adult HLH outcome between different quartiles. b The percentage of adult HLH outcome, stratified according to quartiles of serum ferritin decrease
Fig. 4
Fig. 4
Adult HLH predictive outcome and actual outcome in the validation cohort. a Comparisons of adult HLH outcome between predictive outcome and actual outcome. b The percentage of actual adult HLH outcome, stratified according to quartiles of ferritin decrease
See this image and copyright information in PMC

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