Background Hyperferritinemia is associated with systemic inflammation and adverse clinical outcomes. Its prognostic significance in patients with hematologic malignancies remains underexplored.

Methods We conducted a retrospective cohort study at a single tertiary care center including adult inpatients from October 1, 2015, to October 1, 2023, with an elevated ferritin level >500 ng/mL. Patients were stratified by ICD codes to identify underlying hematologic malignancies. Outcomes were compared within this subgroup based on ferritin levels (<10,000 vs. ≥10,000 ng/mL). Outcomes were also compared between patients with and without hematologic malignancies.

Results Among 4,327 hospitalized patients with hyperferritinemia, the mean age was 63.1 years (SD 16.1), with a slight male predominance (61.1%). Most patients were White (79.4%) and non-Hispanic (94.8%). The median BMI was 28.8 (IQR 24.1–34.5), indicating that obesity was common. Regarding lifestyle factors, 14.8% were current or passive smokers, 41.9% had quit smoking, and 27.8% reported alcohol use. When stratified by ferritin levels, patients with ferritin ≥10,000 ng/mL were more likely to be male (66.1% vs. 60.9%), slightly younger (mean age 60.3 vs. 63.2 years), and more likely to be current smokers (17.8% vs. 14.7%).

Among 4,327 patients with hyperferritinemia, 562 (13%) had hematologic malignancies, of whom 22 (3.9%) had ferritin levels ≥10,000 ng/mL. Patients with ferritin ≥10,000 ng/mL had markedly worse outcomes compared to those with lower levels. In-hospital mortality was 31.8% vs. 14.4%, 30-day mortality was 36.4% vs. 25.4%, and 90-day mortality was 13.6% vs. 11.3%. Median hospital length of stay was longer (11.5 vs. 8.0 days), and ICU admission was more frequent (50.0% vs. 35.7%) in the ≥10,000 ng/mL group. Overall, elevated ferritin ≥10,000 ng/mL was associated with significantly higher mortality and increased ICU utilization among patients with hematologic malignancies.

Patients with hematologic malignancies (N=562) had significantly higher 30-day (25.8% vs. 18.9%, p=0.001) and 90-day mortality (11.4% vs. 6.8%, p=0.001) compared to those without hematologic malignancies (N=3765). Although in-hospital mortality was numerically higher in patients with hematologic malignancies (15.1% vs. 13.2%), this difference was not statistically significant (p=0.475). Median hospital length of stay was longer in the hematologic malignancy group (9 vs. 7 days, p=0.010), whereas ICU admission rates were comparable between groups (36.3% vs. 35.9%, p=0.885). Interestingly, ICU length of stay was shorter among patients with hematologic malignancies (median 3.00 vs. 4.00 days, p=0.006).

Conclusion In hospitalized patients with hematologic malignancies, hyperferritinemia, especially ferritin ≥10,000 ng/m, is strongly associated with poor outcomes, including increased short-term mortality and ICU resource utilization. Ferritin may serve as a useful prognostic biomarker in this population. Patients with extreme hyperferritinemia also exhibit distinct epidemiologic patterns, such as younger age, higher rates of smoking, and male predominance.

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2025
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