Value Of Serum Ferritin Levels Research Articles

Iron Overload in Children With Leukemia; Identification of a Cutoff Value for Serum Ferritin Level.

To determine the prevalence of iron overload in children with acute lymphoblastic leukemia (ALL) after treatment cessation and establish a cutoff value for serum ferritin level as an indicator of iron overload. Early detection and monitoring of iron overload in patients with leukemia is crucial. In this prospective cohort study, 66 pediatric patients with ALL who were treated at a tertiary referral center affiliated with Shiraz University of Medical Sciences in Shiraz, Southern Iran, were investigated from July 2020 to December 2022. Serum ferritin levels were measured 6 months after treatment completion. T2* magnetic resonance imaging of the liver and heart was done for all patients. The receiver operating characteristic curve was used to illustrate the area under the receiver operating characteristic curve to assess the diagnostic value of serum ferritin level and total transfusion volume. A total of 24 patients (36.4%) had iron overload in the heart or liver based on T2 magnetic resonance imaging findings. Serum ferritin level was a highly accurate diagnostic marker for iron overload in pediatric patients with ALL, with a sensitivity of 95.8%, and specificity of 85.7% for a cutoff value of 238.5 ng/mL. Also, blood transfusion was a good predictor of iron overload a sensitivity of 75% and specificity of 81% for a cutoff value of 28.3 mL/kg. We identified specific cutoff values for serum ferritin and blood transfusion volume to predict iron overload with high sensitivity and specificity. These markers offer a cost-effective and accessible approach for periodic screening of iron deposition, particularly in resource-constrained settings.

Study of the relationship of serum Vitamin D and ferritin levels in children with attention deficit hyperactivity disorder

Background: Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent mental health disorders among school-age children in India. Etiopathogenesis is attributed to abnormal dopamine regulation which is influenced by both genetic (genes encodingdopamine-DRD4, DRD5, and DAT1) and environmental factors. Micronutrients such as iron and Vitamin D play imperative roles in neurologic function, neurotransmitter synthesis, and regulation. Aim: The aim of the study was to study the association between Serum Vitamin D and Serum Ferritin levels in children with ADHD. Materials and Methods: This case–control study was conducted in the outpatient department of a tertiary care hospital, from October 2019 to May 2021. Subjects (n=30) included patients with the diagnosis of ADHD (using child behavior checklist and INDT–ADHD). Healthy children of the comparable age group were taken as controls. Statistical analysis was performed using Statistical Package for the Social Sciences software version 22. Results: The mean value of serum ferritin levels in cases was observed to be 32.55±31.97 ng/ml and in controls was 143.43±260.40 ng/ml. The study found a significant difference in the mean value of serum ferritin levels in cases and controls (p?0.024). No significant difference in the mean value of serum Vitamin D in cases and controls (p–0.229) was noted. Conclusions: An association between low levels of serum ferritin and ADHD was seen.

Хроническая болезнь почек и анемия: применение хелата бисглицината железа для коррекции железодефицита у пациентов с хронической болезнью почек

Анемия, имеющая эритропоэтин- и железодефицитный характер, является составляющей хронической болезни почек. Рекомендации KDIGO 2012 определяют анемию как концентрацию гемоглобина < 120 г/л у женщин и < 130 г/л у мужчин. Дефицит железа встречается у более 50 % пациентов с недиализзависимой хронической болезнью почек и у большей части пациентов, получающих диализ. Для диагностики железодефицита используют определение сывороточного уровня ферритина и насыщения трансферрином. Снижение любого из этих показателей является основанием для коррекции гемоглобина соединениями железа. Дефицит железа увеличивается при имеющемся воспалении, потребность в нем возрастает при лечении эритропоэтином. Среди пероральных молекул лучший профиль для всасывания имеют двухвалентные соли железа или те, которые не гидролизуются, имеют высокую биодоступность и хорошо корригируют дефицит железа. В статье рассмотрен Текнофер в качестве примера соединения, имеющего определенные преимущества в коррекции железодефицита при анемии у пациентов с хронической болезнью почек.

Correlation Between Serum Ferritin Level and Vitamin D Hydroxycholecalciferol (25OH) Level in Children with Transfusion Dependent Thalassemia

Background: Transfusion dependent thalassemia (TDT) patients will progressively experience iron overload due to repeated blood transfusions. It also causes vitamin D hydroxycholecalcoferol (25OH) depletion in the liver parenchyma. Methods: This was a cross-sectional study of children with TDT in Hemato-oncology outpatient clinic, Dr. Soetomo Hospital Surabaya which has enrolled in the study from January-june 2020. Serum ferritin level by Enzym linked Fluorescent Assay (ELFA) and vitamin D hydroxycholecalciferol (25OH) level was examined by the ADVIA centaur VitD assay method. To determine the correlation between serum ferritin level and vitamin D hydroxycholecalciferol (25OH) Spearman correlation was used, significant if p<0.05 Results: There were 11 boys and 19 girls with TDT, their age ranged between 7-18 years old. The mean value of serum ferritin level was 2570 (SD 1805.6) ng/ml, and serum vitamin D hydroxycholecalciferol (25OH) was 16 (SD 8.06) nmol/ml. 26/30 subjects had serum ferritin level > 1000 ng / ml, 12/30 subjects were considered deficient in vitamin D hydroxycholecalciferol (25OH), with vitamin D hydroxycholecalciferol (25OH) level <15 nmol/ml. The serum ferritin level had a negative correlation with vitamin D hydroxycholecalciferol (25OH) level (r = -0.476; p <0.008). Conclusion: Increased serum ferritin followed by decreased vitamin D hydroxycholecalciferol (25OH) in children with TDT

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

BackgroundHemophagocytic 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).ResultsMultivariate 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.ConclusionsThese results suggest that the serum ferritin level can be used as an independent prognostic marker in the adult HLH patients.

Concomitant Iron Deficiency with B-Thalassaemia Minor in Preschool Children in Erbil City

Background and objectives: Iron deficiency anaemia and beta thalassaemia trait are the most common microcytic hypochromic anaemias, however, coincidence of both has been the topic of few studies. This study carried out to determine if iron deficiency coexists and to which extent, also influence on hemoglobinA2 level and link to demographical and biochemical parameters among ?-thalassemia trait children aged 1 to 5. Methods: A cross-sectional observational study conducted on 112 children with thalassaemia minor diagnosed by blood counts and hemoglobin electrophoresis. The iron status of all children was measured, those with a cut-off value of serum ferritin level &lt;15 ?g/l considered to have coexistence of iron deficiency (group I), furthermore, different variables compared to the remaining children with normal serum ferritin levels (group II). Results: Out of 112 ?-thalassemia trait children, 39 (34.82%) had concomitant iron deficiency, 35.9% females, and 64.1% males, with no significant difference in sex between the two groups. The mean age ± SD was 38 ± 16 months, yet iron deficiency coincidence was significantly higher among the younger children. There was no significant difference between those with or without iron deficiency regarding hemoglobin A2 level. Conclusions: We found that more than one-third of children with thalassemia minor are also iron deficient. Furthermore, serum ferritin level didn’t impact the hemoglobin A2 in thalassaemic minor children with or without concomitant iron deficiency.

Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine

Iron overload has been associated with poor overall survival in patients with higher-risk myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation, but has not been investigated in higher-risk MDS patients treated with hypomethylating agents. We evaluated the prognostic value of serum ferritin levels at diagnosis in a retrospective analysis of 48 patients with an intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score treated with azacytidine. overall survival probability at 1 and 2 years was 58% and 42%, respectively. When stratifying according to serum ferritin level at azacytidine initiation, patients with serum ferritin level <725 ng/mL had significantly better OS than those with serum ferritin level ≥725 ng/mL, with an overall survival probability of 74% (95% confidence interval [CI]: 58-94) versus 44% (95% CI: 28-68) at 1 year and 57% (95% CI: 39-81) versus 28% (95% CI: 15-52) at 2 years, respectively (p = 0.034). Median progression-free survival was 16.15 months (range: 9-26) for the entire cohort. Progression-free survival probabilities according to serum ferritin cut-off level <725 ng/mL or ≥725 ng/mL at 1 and 2 years were 70% (95% CI: 53-91) versus 44 (95% CI: 28-68) and 52% (95% CI: 35-77) versus 24% (95% CI: 12-48), respectively (p = 0.031). We have demonstrated that an serum ferritin level ≥725 ng/mL was associated with worse overall survival and progression-free survival when adjusting for other covariables in multivariate analysis, in addition, unfavorable karyotype led to worse outcome. In conclusion, we believe that that negative effect of serum ferritin level on overall survival is not only related to the iron toxicity, but most probably may also be considered as a surrogate marker for very ineffective erythropoiesis leading to marked anemia.

Correlation between Serum Ferritin Level and Histopathological Disease Severity in Non-alcoholic Fatty Liver Disease.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Recently several parameters, such as serum ferritin, have emerged as possible predictors for the severity of NAFLD and insulin sensitivity. We aimed to investigate the value of serum ferritin level as a useful biomarker for the prediction of histopathological disease severity in non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of NAFLD. METHODS This was a prospective cross sectional study in which demographic, clinical, histological, laboratory, and anthropometric data of 30 adult patients with biopsy-proven NAFLD/NASH were analyzed. RESULTS In our patients population with mean age of 37.9 years and mean BMI of 26.5, statistical analysis did not show a significant difference between the three grades of steatosis in the mean ferritin levels (p = 0.559). It was also observed that ferritin level did not have a significant correlation with the stage of fibrosis (p = 0.228). The mean transferrin saturation did not show significant difference in different stages and grades of NASH (p = 0.260 and 0.944, respectively), either. CONCLUSION Serum ferritin level may not be useful as a single marker for the prediction of histopathological severity of disease in young patients with NASH who are not morbidly obese.

Serum ferritin as an indicator of the development of encephalopathy in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome

To investigate the diagnostic value of serum ferritin levels as a marker of disease activity and the development of encephalopathy in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli. Twenty patients with HUS were studied. Serum ferritin levels were compared with clinical features and serum soluble tumor necrosis factor receptor (sTNFR) I and sTNFRII levels. Serum sTNFRI and sTNFRII levels were quantified by enzyme-linked immunosorbent assays. Serum ferritin levels were significantly elevated at the time of the diagnosis of HUS. Serum ferritin levels were significantly elevated in patients with encephalopathy compared to patients without encephalopathy. HUS patients with serum ferritin levels of >687.5ng/ml were at high risk of encephalopathy. Serum ferritin levels were significantly positively correlated with serum sTNFRI and sTNFRII levels. Serum ferritin levels are a promising indicator of the development of encephalopathy in HUS.

Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease

Objectives: The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap. Furthermore, there have been no definitive biomarkers for these diseases, making clinical diagnosis difficult. The purpose of this study was to investigate the diagnostic value of serum ferritin levels for differentiating KD from s-JIA and predicting the disease severity of KD.Methods: We analyzed 228 patients with KD and 81 patients with s-JIA. Serum ferritin levels were compared between patients with s-JIA and KD. Furthermore, serum ferritin levels in patients with KD were compared with respect to clinical features such as responsiveness to intravenous immunoglobulin (IVIG) therapy.Results: Serum ferritin levels in KD patients with no response to IVIG therapy were significantly higher than those in KD patients with a good response to IVIG therapy. Serum ferritin levels in patients with KD needing plasma exchange (PE) were significantly higher than those in patients not needing PE. However, serum ferritin levels overlapped between severe KD patients with nonresponsiveness to IVIG therapy or needing PE and other patients with mild KD. Furthermore, patients with s-JIA showed a distinct elevation of serum ferritin levels compared with KD patients. The cutoff value of serum ferritin levels for differentiating KD from s-JIA was 369.6 ng/ml.Conclusions: Serum ferritin levels were significantly elevated in s-JIA patients compared with KD patients. Measurement of serum ferritin levels can be useful for differentiating s-JIA from KD.

Diagnostic Use of Serum Ferritin Levels to Differentiate Infectious and Noninfectious Diseases in Patients with Fever of Unknown Origin

Background and study aim: Fever of unknown origin (FUO) constitutes one of the greatest challenges of clinical practice. It's defined as fever more than three weeks with fever above 38.3oC on several occasions which remains undiagnosed after 3 days of investigations in the hospital or after three outpatient visits. Measurement of ferritin in serum is unfortunately an underutilized diagnostic test in patients with FUO. Highly elevated serum ferritin levels in patients with FUO should prompt further testing to arrive at a specific diagnosis.The aim of this study is to verify the role of serum ferritin levels in differentiation between fever of unknown origin (FUO) caused by infectious and noninfectious diseases. Patients and methods: This study included 40 patients with FUO were hospitalized at Menouf Fever Hospital between July 2013 and June 2014, and 20 volunteers of matched age and gender as a control group. According to the final diagnoses, four causes were identified, including infectious diseases, malignant diseases, collagen diseases and miscellaneous diseases. Laboratory tests, radiological examination and invasive procedures as bone marrow biopsy and lymph node biopsy were done according to cases. Serum ferritin was measured by Human Ferritin ELISA Kit. Results: Of the 40 patients, 20 were caused by infectious diseases, 10 were caused by malignant diseases, 7 were caused by collagen diseases and 3 by miscellaneous diseases (two cases of FMF and one case of drug fever). Serum ferritin levels in infectious diseases was lower than that in noninfectious diseases,where it was 457.6 ng/mL (±248.01) for the infectious disease group and1241.5ng/mL (±1163.80) forthe noninfectious diseases group. Statistically significant difference was found between the two groups (p<0.05). Conclusion: An optimal cutoff value of serum ferritin level >555 ng/mL can predict FUO caused by a noninfectious disease.

Serum Ferritin Level As a Prognostic Marker For Peripheral T-Cell Lymphoma.

BackgroundPeripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and MethodsSerum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. ResultsThe study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P< 0.001), and ferritin levels ≥ 300 ng/ml (P< 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels< 300ng/ml (n = 57; 22% vs. 65%; P< 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. [Display omitted] ConclusionThe serum ferritin level is a useful prognostic marker for PTCL. Disclosures:No relevant conflicts of interest to declare.

Diagnostic Use of Serum Ferritin Levels to Differentiate Infectious and Noninfectious Diseases in Patients with Fever of Unknown Origin

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases.METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed.RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group,p= 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p= 0.049) and between the infectious disease and groups (p= 0.04).CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

Diagnostic use of serum ferritin levels to differentiate infectious and noninfectious diseases in patients with fever of unknown origin.

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases.METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed.RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group, p = 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p = 0.049) and between the infectious disease and groups (p = 0.04).CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

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

Abstract 4466A 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.

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.

AbstractAbstract 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.

Abstract 84: The L-ferritin receptor, Scara5, is expressed on breast cancer and glioma cells: A potential functional significance for cancer-associated high serum/CSF levels

Abstract Elevated levels of circulating ferritin have been associated with several neoplasms, including neuroblastoma, glioblastoma, Hodgkin's lymphoma, and breast cancer. Despite the prognostic value of serum ferritin levels, its role in cancer biology is not understood. Ferritin has long been considered exclusively as an intracellular iron storage protein. However, several lines of evidence have suggested a role for ferritin beyond iron storage, such as angiogenesis, iron delivery, and modulation of the immune response. Recently, a receptor for L-ferritin (the predominant ferritin subunit in the serum and cerebrospinal fluid) has been identified as scavenger receptor class A, member 5 (Scara5). Our preliminary data show Scara5 to be expressed in glioma, neuroblastoma, and breast cancer cells. This novel observation led us to hypothesize that Scara5 internalizes L-ferritin, and serves as a non-transferrin iron delivery mechanism in cancer cells. In support of this hypothesis, we report here that both human liver and human heart ferritins increased cellular survival of the breast cancer cell line MCF-7 in serum free conditions. Taken together, these observations suggest an active functional role for circulating ferritin in tumor biology. The elevated levels of circulating ferritin observed in some cancers may enhance tumor metabolism and growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 84.

Peculiar Hepatocellular Carcinoma Clinical Findings in patients with Thalassemia Syndromes.

Abstract 5108 BackgroundHepatocellular carcinoma (HCC) is the most common primary hepatic cancer, and the fifth and eighth most common malignancy worldwide in men and women, respectively. Hepatitis B and C, primary and secondary hemochromatosis and cirrhosis have been identified as major risk factors. Hepatitis C or B virus infection and secondary hemochromatosis are the major cause of morbidity and mortality. In the last years, HCC on cirrhosis is a common reported complication in patients with thalassemia syndromes1,2,3. In non thalassemia patients HCC is a late complication of cirrhosis and prognosis depends on suitability for treatment. In this group, the last is low (40%) considering that cirrhosis severe stage C, according to Child-Pugh score is generally observed (personal communication). Aim of the studydescribing, in a homogeneous cohort of thalassemia patients, the main clinical findings of HCC. Patients and MethodsAll subjects with risk factors for HCC as iron overloading, HCV or HBV chronic infection, histological evidence of cirrhosis were undergone every six months to an ultrasound evaluation associated with alphaphetoprotein determination. Nine new cases, since January 2000 until July 2009, were detected. Table I shows the main clinical findings. Mean value of serum ferritin levels, in the last 2 years before diagnosis, was 1049±721. All patients except one were anti-HCV positive (Table I). Seven of them were HCV-RNA positive (Table I). None of them had previous HBV infection. ResultsOnly one patient had severe stage C, according to Child-Pugh score. None of the patients had significant high levels of alphaphetoprotein (AFP) at diagnosis. However, a slightly increase of AFP levels was shown, during the 6 months before diagnosis, in 50% of cases. Three patients had a delayed diagnosis because of atypical imaging for HCC at TC scan or a negative previous histology for HCC after liver biopsy. Five patients had multifocal HCC at the diagnosis (Table I). Four showed an unifocal HCC, developing two of them multifocal HCC during the follow-up (Table I). Four patients died during the follow-up for decompensated cirrhosis. Five patients are alive after treatment. Main used treatments are shown on Table I. The overall mean survival was 28±25 months (range 3-64). Conclusions1) almost all talassemia patients with HCC are suitable for treatment ; 2) baseline liver function is the most main factor conditioning survival and suitability for treatment ; 3) periodical serum AFP determnations can reveal a slight increase; 3) iron overloading alone can be related to the development of HCC in a liver with still good functional reserve, giving more opportunity for treatment 4) monitoring for HCC by liver ultrasound evaluation, every six months, in at risk patients with thalassemia syndromes should be mandatory.Table IMain clinical findings of HCC in thalassemia syndromes.PATIENTSSEXPHENO-TYPEAGESURVIVAL FROM DIAGNOSIS (MONTHS)DEADHCV ABHCV RNAUNIFOCAL OR MULTI-FOCAL AT DIAGNOSISFERRITIN (ng/ml)THERAPY1FTM546-++M890TACE2MTM4360+++M1.036TACE3FTI5612+++M1.065TACE SORAFENIB4FTI5923-+-U990TACE5MTI4358-OLT-++U>M2.124RFTA TACE OLT6MTI4818+++M2.262-7FTI6864-++U>M310RESECTION PEI TACE8MTI735---U574PEI TACE9MTM503+++M194SORAFENIBTI: Thalassemia Intermedia; TM: Thalassemia Major; OLT: Orthotopic Liver Transplantation; U: Unifocal; M: Multifocal;Ferritin: mean values in the last 2 yearsPEI: Percutaneous Ethanol Injection; TACE:Transarterial Chemoembolization; RFTA:Radiofrequency Thermal Ablation DisclosuresNo relevant conflicts of interest to declare.

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

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 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml 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 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. 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. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p<0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). 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 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). 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.

Clinical significance of serum iron and ferritin in patients with colorectal cancer.

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 +/- 38.6 micrograms/dl vs 93.0 +/- 32.1 micrograms/dl and 107.1 +/- 32.9 micrograms/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 +/- 35.0 ng/ml (p < 0.01) and 48.8 +/- 72.8 ng/ml (p < 0.001), respectively, vs 117.1 +/- 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85 micrograms/dl and serum ferritin levels below 60 ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.