Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes: Results of a meta-analysis of observational studies

171 Background: Ferritin, an iron storage protein, is elevated in the serum of certain types of cancers, including breast and pancreatic. Ferritin has been shown to play a role in tumorigenesis and cancer cell growth and survival through angiogenesis, immune regulation, and iron delivery. Ferritin may serve as a potential biomarker in evaluating survival of pancreatic cancer patients. Methods: This study determined pretreatment ferritin levels in a phase III clinical trial of 162 patients with advanced pancreatic cancer. A quantitative sandwich ELISA (Human Ferritin ELISA (Assaypro, St. Charles, Missouri) was used to measure pretreatment serum ferritin levels in 162 patients with advanced pancreatic cancer. Serum ferritin level was correlated with overall patient survival using log-rank regression and Kaplan-Meier analysis on a continuous and categorical dichotomous basis (median cutpoint). Results: The median pretreatment serum ferritin in 162 patients was 832.6 ng/ml, a 25th and 75th percentile of 446 and 1735 ng/ml, respectively, and ranged from 51 ng/ml to 35914 ng/ml. When analyzed on a continuous basis, patients with higher serum ferritin had reduced overall survival (p= 0.001). When analyzed on a categorical basis (median 832.6 ng/ml), patients with higher ferritin had shorter overall survival (median 121 days vs. 180 days) (p=0.003). In multivariate analysis with pretreatment serum ferritin, TIMP-1, uPA, and VEGF, TIMP-1 remained the only significant predictive factor (p<0.0001), with ferritin trending toward significance (p= 0.076). Conclusions: Pretreatment serum ferritin in 162 patients with advanced pancreatic cancer was quantified using ELISA. Pretreatment serum ferritin predicted for significantly shorter overall survival in a phase III trial of metastatic pancreatic cancer. Pretreatment serum ferritin level has prognostic biomarker utility in pancreatic cancer, and should be evaluated as a predictive factor for response to novel treatment regimens.

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Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Translational Neurodegeneration ◽

10.1186/s40035-020-00228-9 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Yangfan Cheng ◽

Yongping Chen ◽

Huifang Shang

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Energy Metabolism ◽

Serum Ferritin ◽

Iron Homeostasis ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Meta Analysis ◽

Biochemical Indicators ◽

Als Patients ◽

Lateral Sclerosis

AbstractAccumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.

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A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox In Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 mri.

Blood ◽

10.1182/blood.v116.21.1125.1125 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1125-1125

Author(s):

Yoo-Hong Min ◽

Hyeoung Joon Kim ◽

Kyoo-Hyung Lee ◽

Jae Hoon Lee ◽

Hee-Sook Park ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Myelodysplastic Syndromes ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Transfusion Requirement ◽

Ferritin Level ◽

Iron Chelation ◽

Dry Weight ◽

Mean Value

Abstract Abstract 1125 Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 97 patients with de novo MDS (n = 44) or idiopathic AA (n = 53) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a mean of 28.6 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (8.3%), 25 (69.4%), and 4 cases (11.1%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64.2%) were severe form. Mean value of serum ferritin level in enrolled patients was 3,482.6±436.7 ng/ml in MDS, and 3,904.4±399.2 ng/ml in AA at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 20.8 ± 3.5 mg Fe/g dry weight in MDS and 22.6 ± 2.2 mg Fe/g dry weight in AA. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. Over the study period, patients with MDS and AA received a mean of 24.2 and 22.0 units RBC per year, respectively. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,045.1±446.5 ng/ml and 2,614.7±311.9 ng/ml (p=0.005) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 55 cases, and at the end of study (EOS), the LIC were significantly decreased to 14.3±2.9 mg Fe/g dry weight (p=0.05) and 15.3±2.3 mg Fe/g dry weight (p=0.001) in MDS and AA, respectively. The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 30.9% cases because of death, patient refusal, and decrease in the serum ferritin level below 500ng/ml. All death was ascribed to disease-related causes. This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient's transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Value for Survival of Serum Ferritin Levels Over Time After Allogeneic Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4466.4466 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4466-4466

Author(s):

Mika Nakamae ◽

Hirohisa Nakamae ◽

Hideo Koh ◽

Takahiko Nakane ◽

Mitsutaka Nishimoto ◽

...

Keyword(s):

Overall Survival ◽

Serum Albumin ◽

Cell Transplantation ◽

Serum Ferritin ◽

Prognostic Value ◽

Acute Inflammation ◽

Serum Ferritin Level ◽

Hematopoietic Cell Transplantation ◽

Ferritin Level ◽

The Impact

Abstract Abstract 4466 A significant association between iron overload prior to allogeneic hematopoietic cell transplantation (HCT) and worse prognosis following HCT has been reported. In most previous reports, the serum ferritin level before HCT was used as a surrogate marker of iron load. However, serum ferritin level is known to be increased by acute inflammation, including that due to infection, and/or active hematological diseases. The prognostic value of serum ferritin level has not been evaluated taking into consideration the influence of acute inflammation. In addition, little is known about changes in serum ferritin levels following HCT or the prognostic value for survival after HCT, particularly in the late period post HCT. Here we comprehensively evaluated the impact of serum ferritin level after HCT as well as pre HCT on survival. We retrospectively studied 204 evaluable patients who had undergone HCT in our institute between February in 2004 and December in 2011, and who had available serum ferritin data pre HCT (median age 46, males 114 and females 90). The median follow-up period among surviving patients was 1023 days. We analyzed the impact of serum ferritin level pre HCT on overall survival after adjusting for various positive and negative acute phase reactants including haptoglobin, fibrinogen, CRP and serum albumin levels in multivariate analysis. On univariate analysis, serum ferritin level pre HCT significantly affected overall survival (ferritin per 100 ng/ml, HR: 1.003, p=0.008) and overall survival significantly worsened as serum ferritin level pre HCT increased (p for trend =0.01). However, after adjustment for haptoglobin or serum albumin levels, the relationship between serum ferritin pre HCT and survival was no longer statistically significant. Disclosures: No relevant conflicts of interest to declare.

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Adverse Impact Of Elevated Pretransplantation Serum Ferritin Levels On Survival and Nonrelapse Mortality After Allogeneic Hematopoietic Stem Cell Transplantation In Children

Blood ◽

10.1182/blood.v122.21.2168.2168 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2168-2168

Author(s):

Osamu Kondo ◽

Kohei Higuchi ◽

Mariko Shimizu ◽

Azusa Mayumi ◽

Kanako Isaka ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Pediatric Patients ◽

Ferritin Level ◽

Adverse Impact ◽

Significant Prognostic Factor ◽

Significant Difference

Abstract Background Previous studies showed an association between iron overload and hematopoietic transplant complications. Serum ferritin is widely used as an indicator for iron stores and an elevated pretransplantation level was strongly associated with inferior outcomes of transplantation in adults, though it has not been clarified well in pediatric patients. We studied prognostic impact of pretransplantation elevated ferritin levels on outcomes of allo-HSCT for pediatric hematological diseases. Patients and Methods We studied 93 consecutive pediatric patients (< 18 years old) with hematologic disease who underwent allogeneic HSCT at Osaka Medical Center and Research Institute for Maternal and Child Health between 2003 and 2009 in whom pretransplantation serum ferritin levels were available. The patients were divided into two groups, pretransplantation serum ferritin level ≥ 1000 ng/mL (SF≥1000) and ferritin level < 1000 ng/mL (SF<1000). Survival rate was estimated using the Kaplan-Meier method and compared between the two groups using the log-rank test. The association of pretransplantation ferritin and the transplant outcomes was evaluated in multivariate analysis with Cox proportional-hazards regression model. Results At 5 years after transplant, children in SF≥1000 (n=51) had a significantly lower overall survival (OS; 42.1% vs 76.6, p=0.001) and a higher non-relapse mortality (NRM; 41.0% vs 18.6%, p=0.018) than those in SF<1000 (n=42). SF≥1000 (n=20) in patients with leukemia in nonCR had lower OS (14.4% vs 75.0%, p=0.051) than SF<1000 (n=5), whereas patients in CR had almost the same OS (65.8% vs 62.2%, p=0.920) between SF≥1000 (n=14) and SF<1000 (n=14), although the sample size was too small to detect statistically significant difference. Univariate analyses revealed elevated ferritin level, leukemia, nonCR, GVHD grade 3-4 and haploidentical donor as significant worse prognostic factors for OS and cord blood transplant as a significant better factor. In multivariate analysis, an elevated pretransplantation serum ferritin level was the only significant prognostic factor for worse overall survival [HR(95%CI): 2.35 (1.05-5.27), p=0.038]. There was no significant difference in the incience of acute GVHD, infection and any other complications as causes of nonrelapse death between the two groups, although the total incidence of fatal transplant-related complications was significant higher in SF≥1000. Conclusion Our results indicate that an elevated pretransplant serum ferritin level adversely affects outcomes of allogeneic transplantation in pediatric patients as reported in adults. The adverse impact of elevated ferritin levels on survival resulted from increased NRM. The association between high ferritin levels, which are usually caused by iron overload, and outcomes of transplantation in pediatric patients requires further prospective studies. Disclosures: No relevant conflicts of interest to declare.

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PREDICTIVE SIGNIFICANCE OF HIGH SERUM FERRITIN LEVELS IN THE DEBUT OF MALIGNANT LYMPHOMA

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-12-74-81 ◽

2020 ◽

pp. 74-81

Author(s):

Babaeva T.N. ◽

Seregina O.B. ◽

Pospelova T.I.

Keyword(s):

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Prognostic Significance ◽

Average Concentration ◽

High Serum ◽

Control Group ◽

Malignant Neoplasms ◽

Significant Prognostic Factor ◽

Malignant Lymphomas

At present, the serum ferritin level is not included in the list of prognostic factors; however, it is known that its increased serum level in patients with malignant neoplasms relates with the tumor burden, the degree of disease activity and correlates with a worse prognosis in patients with hematologic malignancies.The normalization of serum ferritin level during remission period confirms the involving of hyperferritinemia in mechanisms of tumor progression and may testify for clinical importance of measurement of serum ferritin level in patients, including those with malignant lymphomas. Objective:The aim of this study was to assess of the prognostic significance of high ferritin levels at the onset of the disease in patients with malignant lymphomas. Materials and methods:98 patients with malignant lymphomaswere enrolled in this study, including 72 patients (73.5%) with non-Hodgkins lymphomas (NHL) and 26 patients (26.5%) with Hodgkin’s lymphoma (HL). The increased serum ferritin level (more than 350 ng/ml) was found in 53 (54.2%) patients with malignant lymphomas at the onset of disease and its average concentration was 587,62±131,6 ng/ml (8.3 times higher values of control group, p<0.001).Also the positive statistical correlationsbetween increased ferritin level and increased level of LDH (r=0.47, p<0.001, n=98) and C-reactive protein (r=0.41, p<0.001, n=98) as well as the presence of B-symptomswere found. The median OS was significantly shorter in the group of patients with increased ferritin level (more than 350 ng/ml) at the onset of disease in comparison with group of patients with normal ferritin level, where the median OS was not reach during the observation period. Patients with increased ferritin level before starting chemotherapy also showed worse results of overall survival and increased mortality risk (OR 8.122; 95% CI, 1.764-37.396;р<0.05) compare with a group of patients with ferritin level ˂350 hg/ml at the onset of disease. Conclusion:These results make it possible to include lymphomas’s patients with increased ferritin level at the onset of disease in the group with poor prognosis and lower OS, while the increased ferritin level in patients without previous blood transfusions should be considered as a significant prognostic factor.

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Relation of Serum Ferritin Level with Serum Hepcidin and Fucose Levels in Children with β-Thalassemia Major

Hemoglobin ◽

10.1080/03630269.2021.1898419 ◽

2021 ◽

Vol 45 (1) ◽

pp. 69-73

Author(s):

Salah H. AL-Zuhairy ◽

Mohammed A. Darweesh ◽

Mohammed A-M. Othman

Keyword(s):

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Thalassemia Major ◽

Serum Hepcidin

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Clinical significance of serum ferritin level as an independent predictor of insulin resistance in Korean men

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2014.08.022 ◽

2015 ◽

Vol 107 (1) ◽

pp. 187-193 ◽

Cited By ~ 7

Author(s):

Sung Keun Park ◽

Won Joon Choi ◽

Chang-Mo Oh ◽

Min-Gi Kim ◽

Woo Taek Ham ◽

...

Keyword(s):

Insulin Resistance ◽

Clinical Significance ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Independent Predictor ◽

Ferritin Level

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Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Disease Markers ◽

10.1155/2018/8309015 ◽

2018 ◽

Vol 2018 ◽

pp. 1-17 ◽

Cited By ~ 7

Author(s):

Shree Ram Lamichhane ◽

Thanuja Thachil ◽

Paolo De Ieso ◽

Harriet Gee ◽

Simon Andrew Moss ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Subgroup Analysis ◽

Meta Analysis ◽

Small Cell ◽

Cancer Tissue ◽

Small Cell Lung

Background. MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. Materials and Methods. All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. Result. Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39–1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC. Conclusion. miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

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