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

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.

A novel prognostic model for adult patients with Hemophagocytic Lymphohistiocytosis

“…Lin et al showed that the pediatric HLH patients with ferritin levels decline ≥96% had a 17-time probability of survival when a comparison was made with ferritin levels fall <50% [26]. Similarly, our study also confirm that the higher post-treatment ferritin (≥1056.1 μg/L) is associated with higher odds of death in adult HLH patients, which is consistent with our previous study: post-treatment ferritin could be served as an prognostic factor in the adult HLH patients [27].…”

Ferritin index is a strong prognostic marker in adult hemophagocytic lymphohistiocytosis

“…There is also an adverse correlation between ferritin decrease and over‐survival in adults and children 14 . Our previous study also displayed that high levels of discharged ferritin or low levels of ferritin change are adverse factors to predict the survivour of adult HLH 15 …”

“…14 Our previous study also displayed that high levels of discharged ferritin or low levels of ferritin change are adverse factors to predict the survivour of adult HLH. 15 The above studies displayed a relationship between ferritin parameters and mortality in patients with HLH and ferritin values are from admission, hospitalisation and discharge. However, there are few studies investigating the roles of ferritin parameters in a study and making a comparison within them.…”

Increased levels of serum interleukin-10 are associated with poor outcome in adult hemophagocytic lymphohistiocytosis patients

“…Anna et al [ 25 ] found that various parameters, including low platelet counts, low hemoglobin levels, high alanine aminotransferase levels, high bilirubin levels, low albumin levels, high ferritin levels and low fibrinogen levels, were predictive of survival outcomes in adults with non-malignancy associated secondary HLH. Moreover, Zhou et al [ 26 ] found that post-treatment serum ferritin ≥ 1050 µg/L may serve as an independent prognostic biomarker in adult HLH patients. Similar to previous studies, we found that low hemoglobin level (< 8.2 g/dL), low platelet counts (< 40 × 10 9 /L), low albumin concentrations (< 28 g/L), high LDH levels (≥ 700 U/L) and high post-treatment serum ferritin levels (≥ 1050 µg/L) were associated with poor survival.…”