Blood Levels of Ferritin Post-Treatment May Predict Survival in Adults

Blood Levels of Ferritin Post-Treatment May Predict Survival in Adults

The amount of ferritin, a protein that stores iron, in the blood after treatment for hemophagocytic lymphohistiocytosis (HLH) may help predict outcomes for adult patients, regardless of the underlying cause of the disease, a study suggests.

A greater decrease in serum ferritin levels from beginning to end of treatment is also associated with a better overall survival, supporting the use of ferritin as a prognostic marker for adult HLH patients.

The study, “Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis,” was published in the Orphanet Journal of Rare Diseases.

HLH is a rare and life-threatening disease, in which certain white blood cells are unusually active and damage organs. The disease most commonly appears in children as a result of a faulty gene (primary HLH), but up to 40% of HLH cases occur in adults, in which conditions like infections, cancer, or autoimmune disease are the most likely underlying cause (secondary HLH).

While adult HLH has a poor prognosis, no biomarker exists that helps doctors accurately identify those at higher risk of death, who may benefit from more intensive management.

Ferritin is a protein that binds and stores iron inside cells, but is released into the serum (the liquid component of blood) in the presence of inflammation. Serum ferritin is among the parameters examined in blood tests used to diagnose HLH, but its prognostic value in adults with the condition remains uncertain.

Researchers in China conducted a retrospective observational study to determine if ferritin blood levels could be used to predict overall survival for adult patients who recently started treatment.

They examined two groups of patients: a test group to determine the best ferritin cut-off value to predict survival, and a validation group where this cut-off value was confirmed.

The test group included 161 people, with a median age of 49 at diagnosis, and whose HLH was caused mostly by an infectious disease (35.4%), followed by cancer (24.2%), and autoimmune diseases (4.9%).

Levels of ferritin in this group ranged from 188 to over 15,000 micrograms per liter (mcg/L), with most patients (92.81%) exhibiting levels above the cut-off value for a diagnosis of HLH (more than 500 mcg/L).

The median overall survival of the test group was 12 weeks, with a one-year mean overall survival of 36.6%. Preliminary analysis showed that the higher the levels of ferritin, the poorer was the survival rate.

Researchers then established a serum ferritin level below 1050 mcg/L as the best predictor of patients living past the one-year mark. In fact, only 28% of patients with a serum ferritin above that cut-off survived for one year or more.

This cut-off could also be applied to subgroups with different underlying causes. Across subgroups, more than 80% of patients whose ferritin levels were below the cut-off lived for at least one more year. In contrast, a serum ferritin level above the cut-off was associated with a 25% survival rate for those with cancer-associated HLH after one year, and a 17% survival rate for those with infection-associated HLH.

In this analysis, HLH due to autoimmune diseases was not tested due to a small patient group.

The team then validated their findings in a second group of 68 people (validation group), that was similar to the first group in most clinical and demographic features, except for their age (median of 55 years) and lower levels of calcium.

In this group, serum ferritin levels after treatment remained independently associated with survival, and still predicted patients’ survival with high accuracy.

A greater decline in ferritin levels from before to after treatment was also predictive of better survival rates. Patients whose levels dropped by more than 81% had significantly better survival rates at six months (94%) than those whose levels increased by 14% or more (31% survival rate).

Based on the results, the team concluded that “post-treatment serum ferritin level can serve as an independent prognostic biomarker associated with early death, poor [overall survival] regardless of the underlying etiology for the adult HLH patients.”

Nonetheless, researchers noted that the retrospective nature of their study, and its small sample size, are clear limitations. “[M]ulticenter prospective randomized clinical trials with larger sample size are needed to further verify our results,” they wrote.

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