Different Adverse Event Profiles and Significant Hematological Improvement Are Noted When Deferasirox Was Used in Adult Patients with Chronic Transfusion-Related Iron Overload in Taiwan: Results from a Prospective Observational Clinical Trial

Abstract Background Iron overloading is a common problem for adult with myelodysplastic syndrome (MDS), aplastic anemia (AA) or other chronic anemia. Deferasirox (DFX) has been proven as an effective therapy to chelating iron in these patients. Anyway, the safety of DFX is still a concern, and the information of safety profiles and efficacy are less understood in Taiwan. This study is planned primarily to collect long-term safety data of DFX treatment in iron-overloaded MDS, AA and other chronic anemia patients in Taiwan. Study Design This is an observational, single-arm, and multi-center study. Low-risk MDS or AA patients with transfusion-related iron overload, or patients with other anemia and serum ferritin more than 2000 ug/ml, were enrolled within the 18-month enrolling period if DFX is planned to be prescribed. Exposure of iron chelating agents other than DFX before trial initiation was allowed. The initial dose and subsequent adjustment of DFX were up to investigator¡¦s preference. All patients were followed for 3 years for adverse events (AEs) and disease outcomes. Results From 2009 to 2011, 79 patients were enrolled in this study, including 38 MDS, 23 AA and 18 other chronic anemias. Forty-seven cases (59.5%) were male, with mean age 64.3¡Ó17.8 y/o. Fifty-six (70.9%) subjects failed to complete the 3-year study period, but only 8 (10.1%) of the subjects withdrew DFX due to drug-related AEs. The mean DFX exposure dose during study was 17.7¡Ó4.02 mg/Kg/day. In contrast with those reported in literature, the most frequently reported drug-related AEs were rash (16, 20.3%), diarrhea (11, 14.0%), hypercreatinemia (8, 10.1%), pruritus (7, 8.9%), and so on (as in Table 1). When classified by organ systems, skin disorders were the frequently reported one (26, 32.9%), and followed by GI disorders (n=24, 30.4%). Grade 3-4 drug-related adverse events were rare (n=4, 5.1%). For all subjects, DFX could effectively decrease serum ferritin level from baseline (-985+/-2090 ng/ml (p=0.0154 vs. baseline) and -1710+/-2290 ng/ml (p=0.0424 vs. baseline) at 1 yr and 3 yr, respectively) (as in Figure 1). Notably, after DFX usage, 23 patients (32.4%) developed erythroid response according to IWG 2006 criteria; the mean hemoglobin could increase from 7.77+/-1.63 gm/dl (baseline) to 8.25+/-2.60 gm/dl (at 36 month, p=0.6172 vs. baseline), when the average transfusion amount was decreased from 2.3+/-1.4 units (baseline) to 1.6¡Ó0.5 units (at 36 months, p=0.0406 vs. baseline). (as in Figure 2). Ten patients (10/46, 21.7%) had platelet response. For the 38 MDS patients, DFX also could significantly lower serum ferritin level (-590+/-2490 ng/ml (p=0.4095 vs. baseline) and -1310+/-362 ng/ml (p=0.0013 vs. baseline) at 1 yr and 3 yr, respectively) but seemed to have a less extent than that in overall population. Similarly, 10 patients (21.7%) developed erythroid response after DFX use. The mean hemoglobin increment (from 7.67+/-1.67 gm/dl (baseline) to 8.55+/-3.45 gm/dl (at 36 month, p=0.6012 vs. baseline)) and the decrease of average transfusion amount (from 2.1+/-1.2 units (baseline) to 1.6+/-0.6 units (at 36 months, p=0.2943 vs. baseline) were not significant, probably due to low case number (as in Figure 2). Four (4/19, 21.1%) patients experienced platelet response. Conclusion This study showed that the profiles of AEs regarding DFX use for adult anemic patients with transfusion-related iron overload in Taiwan were significantly different from those reported in Western countries. The AE-related discontinuation rate was also relatively low. An expected efficacy to lowering serum ferritin by DFX, and a significantly degree of hematological improvement was noted, too. Table 1. Drug-related adverse events, for all events with incidences > 5% and all grade 3-4 events: Table 1. Drug-related adverse events, for all events with incidences > 5% and all grade 3-4 events: Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Chang: Novartis: Honoraria.

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Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1392 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Alaa Mutter Jabur Al-Shibany ◽

AalanHadi AL-Zamili

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Iron Level ◽

The Mean ◽

T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

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The Effect of Chronic Viral Hepatitis on Serum Ferritin Level in Thalassemia Patients

Blood ◽

10.1182/blood-2019-125010 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4819-4819

Author(s):

Natthapat Rujeerapaiboon ◽

Adisak Tantiworawit ◽

Pokpong Piriyakhuntorn ◽

Thanawat Rattanathammethee ◽

Sasinee Hantrakool ◽

...

Keyword(s):

Viral Load ◽

Iron Overload ◽

Viral Hepatitis ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Conflicts Of Interest ◽

Ferritin Level ◽

Iron Concentration ◽

Chronic Viral Hepatitis ◽

The Mean

Background: Serum ferritin is widely used as a marker of iron overload in thalassemia patients. However, the ferritin level is affected by active infections or inflammation. The association between viral hepatitis and serum ferritin level in thalassemia patients is still unclear. This study aimed to determine the effect of chronic viral hepatitis on serum ferritin level in thalassemia patients. Methods: This was a cross-sectional study in thalassemia patients aged ≥15 years-old at Chiang Mai University hospital. We expected that thalassemic patients in our clinic have a mean serum ferritin of 767 ng/mL with a standard deviation of 210 ng/mL. As a result, we have to enroll a total of 28 patients to demonstrate 30% difference of mean serum ferritin when the power was set at 80% with alpha level of 0.05. Information on chronic viral hepatitis, mean serum ferritin and liver iron concentration (LIC) as measured by T2* MRI were collected. Chronic viral hepatitis status was confirmed by either HBV DNA or HCV RNA testing. Patients were categorized to hepatitis and non-hepatitis group. Serum ferritin levels were compared between two groups. LIC measurement was used as a gold standard for iron overload. Subgroup analysis was performed according to iron overload and transfusion requirement status. Categorical and continuous variables were compared using the Chi-squared test and T-test, respectively. The correlation between viral loads and mean serum ferritin levels was analyzed by Pearson's correlation. Result: Of 32 thalassemia patients (25 non-transfusion dependent [NTDT] and 7 transfusion dependents [TDT]), 13 patients had chronic viral hepatitis (7 with hepatitis B and 6 with hepatitis C infections). The LIC between hepatitis and non-hepatitis groups were not significantly different (7.28 [SD 4.7] vs 9.08 [SD 5.2] mg Fe/g, p=0.19). In the higher LIC group (≥ 5 mg Fe/g), the mean serum ferritin level was higher in the hepatitis group than non-hepatitis group (1,776 [SD 488] vs 967 [SD 860] ng/mL, p=0.03). For the lower LIC group (<5 mg Fe/g), the mean ferritin levels were not significantly different between the hepatitis and non-hepatitis groups (646 [SD 224] vs 459 [SD 205] ng/mL, p=0.22). The correlation between the viral load and mean ferritin level in NTDT group showed a significant linear correlation with R=0.7 (p=0.04). Conclusions: We observe a higher serum ferritin level among thalassemia patients who concurrently have chronic viral hepatitis. Chronic viral hepatitis is a possible cause of a falsely high ferritin level in these patient population. Furthermore, the viral load is positively correlated with serum ferritin level. Disclosures No relevant conflicts of interest to declare.

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Oral Chelator Deferiprone in Adult with Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.4615.4615 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4615-4615

Author(s):

Ruben Nzouakou ◽

Anoosha Habibi ◽

Ketty Lee ◽

Alain Luciani ◽

Jean-François Deux ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Cardiac Iron ◽

Median Level ◽

Cardiac Iron Overload ◽

The Mean

Abstract Abstract 4615 INTRODUCTION Long-term blood transfusion is essential for patients with sickle cell disease (SCD) in case of cerebral vasculopathy, organ dysfunction, leg ulcer, failure or intolerance of hydroxyurea treatment. Secondary iron overload is a factor of morbidity and mortality by organ damage. In practice, three chelators are available: deferoxamine (DFO) which is administrated by subcutaneous infusion and therefore source of poor compliance in SCD. Deferasirox (DFX), the new oral chelator is the first line therapy since 2007. Deferiprone (DFP) is an option when DFX or DFO are contraindicated or inadequate. However, DFP has no approval for SCD. The purpose of this study is to describe the characteristics of SCD patients treated by DFP. METHODOLOGY The patients included in this study arise from the group of the patients with long-term blood transfusion by manual exchange in Henri Mondor's SCD center, and in whom iron overload is treated by DFP. The monitoring of iron overload is obtained by regular serum ferritin level, combined liver and heart MRI. Only one iron measure by MRI is available for each patient throughout the study. RESULTS Nine patients (8 SS and 1 Sβ0thal) are included: 5 men and 4 women. The mean age is 44.2 years (22 to 64 years). The median duration of chronic transfusion is 10 years (4 to 27 years). The average dose of DFP is 68 mg / kg / day (50 to 93 mg / kg / day). The median follow-up under DFP is 30 months (7 to 60 months). The median level of serum ferritin before the initiation of DFP is 5830 μg / l (1800 to 9300 μg / l); and the median level of serum ferritin at the end point is 7940 μg / l (4540 to 11300 μg / l). MRI shows an important hepatic iron overload (up to 320 μmol) in all patients and one cardiac iron overload (T2* = 12 ms). Three patients stopped DFP and switch to deferasirox (DFX) as soon as DFX was available. For the other patients, the reason of prescribing DFP instead of DFX was renal failure in 5 patients and DFX related GI symptoms in one patient. No agranulocytosis is observed. The weekly then monthly monitoring of blood count is insured for all patients. No cytolysis by drug's toxicity is observed, except for one patient with liver transplant and who has an active HCV infection. DISCUSSION Serum ferritin level is the easiest marker of iron overload follow-up, but is subject of important variations due to inflammation, hemolysis, and cytolysis. Indeed, MRI is the only one reliable measure. The evidence of cardiac iron overload is proved in one patient, and confirms the importance of this measure on SCD patients. This motivates the edition of guidelines concerning the prevention and monitoring of iron overload among these patients. The dosage of DFP remains reasonable compared to the mean dosage use in other pathologies. This dosage depends of the degree of iron overload and the individual tolerance. Data are not sufficient at these days to evaluate the efficacy of DFP to reduce or to stabilize the level of iron overload. However, we observe globally a good clinical and biological tolerance, even in patients who have organ transplant and therefore have several concomitant treatments. CONCLUSION DFP in patients with SCD is globally well-tolerated, but its efficiency is not proved yet. Approval of DFP for SCD is needed. As life expectancy improves in SCD, more patients will require long-term transfusion and thus iron chelation therapy. Cardiac Iron overload is possible in patients with SCD. So, it would be systematically looked after. Disclosures: No relevant conflicts of interest to declare.

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Two-Year Analysis of Efficacy and Safety of Deferasirox (Exjade®) Treatment in Myelodysplastic Syndrome Patients Enrolled in the US03 Study.

Blood ◽

10.1182/blood.v114.22.3829.3829 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3829-3829 ◽

Cited By ~ 7

Author(s):

Alan F. List ◽

Maria R. Baer ◽

David P. Steensma ◽

Azra Raza ◽

Jason Esposito ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Lower Risk ◽

Research Funding ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Efficacy And Safety ◽

The Mean ◽

Neutrophil Response

Abstract Abstract 3829 Poster Board III-765 Introduction A large proportion of patients (pts) with myelodysplastic syndromes (MDS) become dependent on red blood cell (RBC) transfusions, escalating the risk of transfusional hemosiderosis and associated adverse effects. The US03 study was designed to evaluate the long-term efficacy and safety of the oral iron chelator, deferasirox, administered once-daily in pts with lower-risk MDS. 173 pts at 45 centers in the US and Canada enrolled in the 1-year core phase of the study and 83 pts participated in the 2-year extension phase. We now present data from pts who have completed 2 years of deferasirox treatment. Methods US03/E is an ongoing, Phase II, open-label, 3-year trial in pts with Low- or Int-1 IPSS-risk MDS. Eligible pts had transfusional iron overload (serum ferritin ≥1000 μg/L and >20 units of RBC transfusions) with serum creatinine (SCr) ≤2-fold the upper limit of normal (ULN). Initial deferasirox dose was 20 mg/kg/day, which could be increased up to 40 mg/kg/day based on tolerability and response criteria. Serum ferritin and creatinine were monitored monthly. Baseline features 83 pts entered the extension study; mean age was 68 years (range 21–90) with 41 men and 42 women. IPSS risk groups were Low in 23 (28%) pts and Int-1 in 60 (72%). Mean serum ferritin level at the beginning of the extension phase was 2496 μg/L (range 546–7770); mean lifetime number of transfusions was 83.6 (range 20–364) and the mean duration of transfusion therapy was 4.6 (2–12) years. 18 (22%) pts were receiving growth factors (8 darbepoetin, 5 G-CSF, 4 epoetin alpha and 1 tranexamic acid), and 13 pts were receiving other MDS specific therapies (5 decitabine, 4 azacitidine, 3 lenalidomide, and 1 hydroxyurea). The calculated creatinine clearance at extension study entry was normal (>80 mL/min) in 20 (25%) pts and abnormal in 59 (75%), including mild renal insufficiency (51–80 mL/min) in 41 (52%) pts, moderate (30–50 mL/min) in 16 (20%) and severe in 2 (3%). Two-year efficacy results At the time of this analysis, 54 pts completed 2 years of treatment (1 year in the core and one year in the extension portion of the study). Over 24 months, the mean dose of deferasirox was 22.8 mg/kg/day and the mean transfusion rate was 4 units/month. Serum ferritin results are available from 50 pts who have received deferasirox for 100 weeks (Figure). The mean serum ferritin level decreased significantly from study baseline: 3002 to 2069 μg/L at 100 weeks (Δ=933 μg/L; P<0.001, signed rank test). Six (7%) pts experienced hematological improvement according to IWG 2000 criteria. Three patients experienced an erythroid response (major, n=2; minor n=1); only one who achieved a minor response received MDS treatment with darbepoetin. Others included major platelet response (n=1; not receiving MDS treatment), major neutrophil response (n=1; not receiving MDS treatment) and one combined major platelet and neutrophil response while receiving G-CSF and decitabine treatment. Safety Of 83 pts, 35 (42%) discontinued from the study: 8 (9.6%) due to abnormal laboratory values (increase of creatinine 6, thrombocytopenia 1, and neutropenia and thrombocytopenia 1), 8 (9.6%) due to adverse events (gastrointestinal symptoms 3, Clostridium dificile infection 1, renal dysfunction 1, cardiac symptoms 1, unknown 1), 11 (13.2%) due to serious AEs with an outcome of death (none of the deaths were related to deferasirox) and 8 (9.6%) due to MDS progression/AML. Of 67 pts with normal baseline SCr, 24 (30%) had an increase in SCr values above the ULN on at least two occasions (3.0 mg/dL max SCr). Of 16 pts with abnormal baseline SCr, one had an increase to above the ULN on at least two occasions. New onset of grades 3 and 4 thrombocytopenia and neutropenia occurred in 15 (18%) and 29 (35%) pts, respectively. Conclusions In pts with lower-risk MDS and iron overload, deferasirox significantly reduced serum ferritin over 2 years. Deferasirox was generally well tolerated over 2 years. The final year of this study will continue to assess the long-term safety and efficacy of deferasirox in these lower-risk MDS pts with iron overload. Disclosures: Raza: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Esposito:Novartis Pharmaceuticals: Employment. Martinez-Lopez:Novartis Pharmaceuticals: Employment. Paley:Novartis Pharmaceuticals: Employment, Equity Ownership. Besa:Novartis: Research Funding, Speakers Bureau.

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Prospective Evaluation of the Effect of Deferasirox on Hematologic Response in Transfusion-Dependent Patients with Low-Risk MDS and Iron Overload: The Rythmex Study

Blood ◽

10.1182/blood.v128.22.2008.2008 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2008-2008 ◽

Cited By ~ 2

Author(s):

Christian Rose ◽

Olivier Fitoussi ◽

Emmanuel Gyan ◽

Maya Hacini ◽

Shanti Amé ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Transfusion Requirement ◽

Ferritin Level ◽

Low Risk ◽

Erythroid Response ◽

Median Serum ◽

Positive Effect

Abstract Background:Long-term blood transfusions remain the mainstay of supportive care in patients with low-risk myelodysplastic syndromes (MDS). Blood transfusions can result in iron overload, which can lead to impaired organ function, significant morbidity and mortality. Although debate exists around its use in patients with MDS, iron chelation therapy is recommended in patients with low-risk MDS to prevent iron-overload toxicities and to improve survival. In addition, hematologic improvement has been reported during chelation therapy (Jensen PD 1996, Gattermann N 2012). Here we report results from a prospective, observational study that evaluated a hematologic response to deferasirox in a large population of regularly transfused patients with low- or intermediate-1-risk MDS. Methods:inclusion criteria: Transfusion-dependent (at least 4 packed red blood cells (PRBC)/8 weeks) adult patients with IPSS low- or intermediate-1-risk MDS who had initiated or had been receiving chelation therapy for less than 3 months. Primary endpoint was reduction in transfusion requirements at 3 month, (i.e. the number of PRBC received during the 8 weeks before deferasirox initiation compared with the 8 weeks before month 3). Secondary endpoints included: hematologic improvement (HI; IWG 2006 criteria for erythroid [HI-E], platelet [HI-P] and neutrophil [HI-N]) at 3, 6 and 12 months, duration of response, serum ferritin levels and safety. Results: 70 patients were included, 57 were evaluable. Most exclusions (19%) were related to a low level of transfusion before inclusion. Median age was 78.3 years. The cytologic subtypes were: sideroblastic anemia, 31.6%; refractory anemia, 19.3%; refractory anemia with excess blasts-1, 17.5%; refractory cytopenia with multilineage dysplasia, 17.5%; 5q syndrome, 10.5%; unclassified SMD, 3.6%. Median time since diagnosis was 2.79 years (33 months). Before inclusion, 87% patients had received a treatment for MDS (erythropoiesis-stimulating agents, 72%; lenalidomide, 17%;G-CSF, 16%; azacitidine, 7%; thalidomide: 2%). Patients received a median of 5.8 ± 2.8 PRBC during the 8 weeks before inclusion. The mean number of PRBC received per month during the 6 months before inclusion was 2.11. The median serum ferritin level at inclusion was 1 543 ng/ml.The mean number of PRBC received in the whole population post inclusion (eight weeks before month 3) was 5.9, which was not significantly different from the number of PRBC given during the 8 weeks before inclusion (5.8). However at 3 months, 4 patients had a positive effect on transfusion requirement. At 6 and 12 months, positive effect occurred in 3 and 4 additional patients, respectively. 10 patients achieved HI-E during the study and according to Kaplan-meier analysis, the probability of HI-E was 12.7% at 6 months and 24.2% at 1 year. During the study, 17 patients (32%) achieved an erythroid response, i.e positive effect on transfusion requirement and/or HI-E; 19% had an erythroid response at month 12. Median duration of erythroid response was 123 days. 3.5%, 10%, 21% of patients had received a concomitant treatment with deferasirox at 3, 6, and 12 months, respectively. However,deferasirox was the sole specific treatment received in 12/17 patients with erythroid response. 27 patients experienced adverse events (AEs) related to deferasirox, among them 4 patients with grade > 2 . 32 patients underwent deferasirox dosing modifications, and 20 patients had discontinued treatment by 3 months ( median duration of treatment 11.3 months). In patients receiving deferasirox for more than 9 months, the median serum ferritin level at 12 months was 1 438 ng/ml . In contrast, the median serum ferritin level at 12 months was 2247 ng/ml in the whole group. There were no predictive factors of erythroid response (cytologic classification, time since diagnosis, level of ferritin at inclusion, the number of PRBC transfused before inclusion), but the number of responders was low. Conclusions: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused low risk MDS patients. However, deferasirox could induce 19% of specific erythroid response at 12 months. These results suggest that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a small subset of patients with MDS and iron overload. Disclosures Rose: Genzyme, Novartis, Celgene: Honoraria, Research Funding. Beyne-Rauzy:Celgene, Novartis: Honoraria. Dreyfus:Novartis: Honoraria.

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Noninvasive assessment of iron overload by magnetic resonance imaging

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2020-19-3-158-163 ◽

2020 ◽

Vol 19 (3) ◽

pp. 158-163

Author(s):

E. E. Nazarova ◽

D. A. Kupriyanov ◽

G. A. Novichkova ◽

G. V. Tereshchenko

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Concentration ◽

The Body ◽

Iron Accumulation ◽

Resonance Imaging

The assessment of iron accumulation in the body is important for the diagnosis of iron overload syndrome or planning and monitoring of the chelation therapy. Excessive iron accumulation in the organs leads to their toxic damage and dysfunction. Until recently iron estimation was performed either directly by liver iron concentration and/or indirectly by measuring of serum ferritin level. However, noninvasive iron assessment by Magnetic resonance imaging (MRI) is more accurate method unlike liver biopsy or serum ferritin level test. In this article, we demonstrate the outlines of non-invasive diagnostics of iron accumulation by MRI and its specifications.

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Red meat and egg intake and serum ferritin concentrations in Colombian children: results of a population survey, ENSIN-2015

Journal of Nutritional Science ◽

10.1017/jns.2020.5 ◽

2020 ◽

Vol 9 ◽

Author(s):

Oscar F. Herran ◽

Jhael N. Bermúdez ◽

María Del Pilar Zea

Keyword(s):

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Red Meat ◽

Cross Sectional ◽

Egg Consumption ◽

Dietary Consumption ◽

The Mean ◽

The Relationship ◽

Meat And Eggs

Abstract The present study aimed to (a) establish the frequency of consumption of red meat and eggs; (b) determine serum ferritin levels (μg/l); and (c) establish the relationship between serum ferritin and the consumption of red meat and eggs. In Colombia during 2014–2018, an analytical study was conducted in 13 243 Colombian children between the ages of 5 and 17 years, based on cross-sectional data compiled by ENSIN-2015 (Encuesta Nacional de la Situación Nutricional en Colombia-2015) on serum ferritin levels and dietary consumption based on a questionnaire of the frequency of consumption. Using simple and multiple linear regression, with the serum ferritin level as the dependent variable and the frequency of consumption as the main explanatory variable, the crude and adjusted partial regression coefficients (β) between serum ferritin levels and consumption were calculated. The frequency of habitual consumption of red meat was 0⋅49 (95 % CI 0⋅47, 0⋅51) times/d. The frequency of habitual egg consumption was 0⋅76 (95 % CI 0⋅74, 0⋅78) times per d. The mean serum ferritin level in men was 41⋅9 (95 % CI 40⋅6, 43⋅1) μg/l and in women, 35⋅7 (95 % CI 34⋅3, 37⋅7) μg/l (P < 0⋅0001). The adjusted β between the consumption of red meat and eggs and serum ferritin levels were β = 3⋅0 (95 % CI 1⋅2, 4⋅7) and β = 2⋅5 (95 % CI 1⋅0, 3⋅9) for red meat and eggs, respectively. In conclusion, red meat and eggs are determinants of serum ferritin levels in Colombia and, therefore, could be considered public policy options to reduce anaemia and Fe deficiency.

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Tissue doppler imaging in thalassemia major patients: correlation between systolic and diastolic function with serum ferritin level

Paediatrica Indonesiana ◽

10.14238/pi52.4.2012.187-93 ◽

2012 ◽

Vol 52 (4) ◽

pp. 187 ◽

Cited By ~ 1

Author(s):

Syarif Rohimi ◽

Najib Advani ◽

Sudigdo Sastroasmoro ◽

Bambang Mardiyono ◽

Sukman Tulus Putra ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Tissue Doppler Imaging ◽

Negative Correlation ◽

Serum Ferritin Level ◽

Systolic Function ◽

Ferritin Level ◽

Tissue Doppler ◽

Doppler Imaging ◽

Number Of Patients

Background Thalassemia is a major public health problem inIndonesia. Cardiac diseases remain as the main cause of death inthese patients due to iron overload. Although the T2* magneticresonance imaging has been considered as the gold standard forassessing cardiac iron overload but it has limited availability.The tissue doppler imaging (TDI) echocardiography, a fairly newand easy method that is suggested, can detect early abnormalmyocardial iron overload.Objective To assess myocardial systolic and diastolic functionof thalassemic patients using TDI and examine their correlationwith serum ferritin level.Methods A cross􀁌sectional study was conducted from January toMarch 2011 at the Harapan Kita Women and Children Hospital.We performed clinical examination, serum ferritin level, as wellas conventional and tissue doppler echocardiography on allsubjects.Results We included 34 regularly􀁌tranfused patients, of which17 were boys. The mean age of the subjects was 11.6 (SD 4.7years, range 2.6 􀁌 20 years). Mean pulse rate and blood pressurewere within normal range. Hemoglobin level at inclusion rangedfrom 5.8 to 6 g/dL. Almost all patients did not receive regularchelation therapy. Median serum ferritin level was 6275 ng/mL(range 2151 - 17,646 ng/mL). Conventional echocardiographyshowed normal systolic function, but some diastolic dysfunctionswere found including E wave abnormalites in 4 patients, A waveabnormalites in 3, and E/A ratio abnormalites found in 3. TheTDI showed decreased systolic function (Sa wave abnormality) in9 patients and diastolic dysfunctions (Ea wave abnormality in 11patients and Aa wave abnormaly in 2). No abnormality was foundin Ea/Aa and ElEa ratios. There was a weak negative correlationbetween ferritin level and Sa wave and Ea wave respectively anda moderately negative correlation between ferritin level and Ea/Aa ratio. There was no correlation between serum ferritin andAa wave or ElEa ratio.Conclusion TDI identifies a greater number of patients Mthsystolic and diastolic myocardial dysfunction than was revealedby conventional echocardiography. There was a weak negativecorrelation between serum ferritin to Sa wave and Ea wave, and amoderately negative correlation between ferritin and Ea/Aa ratio.There was no correlation between serum ferritin and Aa wave orElEa ratio. [paediatr Indones. 2012;52:187,93].

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Hematologic Improvement with Iron Chelation using therapy Deferasirox in Patients with Aplastic Anemia: A Subgroup Analysis of KAMS0112 Prospective Study,

Blood ◽

10.1182/blood.v118.21.3424.3424 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3424-3424

Author(s):

Yoo-Hong Min ◽

Sung-Soo Yoon ◽

Hyeoung Joon Kim ◽

Kyoo-Hyung Lee ◽

Jae Hoon Lee ◽

...

Keyword(s):

Platelet Count ◽

Iron Overload ◽

Serum Ferritin ◽

Research Funding ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Chelation ◽

Hemoglobin Level ◽

Hematopoietic Stem ◽

Wbc Count

Abstract Abstract 3424 Patients with aplastic anemia (AA) are suffered from various complications related to bone marrow failure and peripheral cytopenia. Although immunosuppressive therapy or hematopoietic stem cell transplantation has been performed for curative purpose, the majority of patients have been treated only by supportive cares including repeated transfusion. However, because continued transfusion eventually induces iron overload in many tissues and organs, transfusional iron overload and its consequences are another life-threatening problems for AA patients. Previous reports about iron chelation therapy (ICT) have mainly shown its efficiency for decreasing tissue iron and safety. However, improvement in hematopoiesis after iron chelation therapy has been limitedly reported as case reports or trials involving small number of patients without objective tools for measuring tissue iron content. In the KAMS0112 study (a multi-center, open label, prospective study evaluating the efficacy of ICT with deferasirox in transfusional iron overload with myelodysplastic syndrome or AA using quantitative R2-MRI, Ferriscan), a total of 54 patients with AA showing serum ferritin level over 1,000 ng/ml were enrolled from 19 institutes, and further analyzed for the changes in hemogram during ICT as well as efficacy and safely of deferasirox. During the study, the specific treatments for AA, such as immunosuppressive therapy or hematopoietic stem cells transplantation, were not undertaken. During 1 year prior to study, patients received 23.7±16.9 units of red blood cell (RBC) product, and the baseline serum ferritin level and liver iron content (LIC) were 4,164±447 ng/ml and 20.1±12.0 mg Fe/g DW, respectively. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin level falls below 500 ng/ml, treatment was withheld. In spite of continued transfusional support during the study, serum ferritin level and LIC were significantly decreased after 1 year of ICT with deferasirox (Ds-ferritin=−3,076.7±489.9 ng/ml, p=0.0003; DLIC=−7.73 mg/Fe/g DW, p=0.001). To evaluate the improvement of each parameter in hemogram by ICT, patients with baseline hemoglobin level less than 8.0 g/dl (n=28), with baseline WBC count less than 4/ml (n=43), and with baseline platelet count less than 20/ml (n=31) were selected separately. At the end of study, hemoglobin level and platelet count (8.2±3.0 g/dl and 22.2±31.4/ml, respectively) was significantly increased from the baseline value (6.1±1.1 g/dl, p=0.001; 12.5±12.4/ml, p=0.05, respectively). WBC count was also slightly increased (from 2.1±0.9/ml to 2.3±0.9/ml, p=0.457). Considering the relatively uniform criteria of transfusion, the finding that hemoglobin level and platelet count could increase above 8 g/dl and 20/ml, respectively, after 1 year of deferasirox treatment is clinically significantly. Due to gradual improvement of anemia, requirement of RBC transfusion had continuously decreased during the study period (R2=0.31). This subanalysis of KAMS0112 study demonstrates that ICT using deferasirox can be effective in improving anemia and thrombocytopenia in the transfusional iron overload patients with AA, as well as reducing serum ferritin level and LIC. Further studies might be required to elucidate the mechanism involved in the improvement of hematopoiesis associated with correction of deranged intracellular iron homeostasis. Disclosures: Min: Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Lee:Novartis: Research Funding. Won:Novartis: Research Funding. Shim:Novartis: Research Funding. Kim:Novartis: Research Funding. Seung:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Chung:Novartis: Research Funding. Hyun:Novartis: Research Funding. Jo:Novartis: Research Funding. Jung:Novartis: Research Funding. Sohn:Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Joo:Novartis: Research Funding. Cheong:Novartis: Research Funding.

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Significant Impact Of Iron Chelation After Allogeneic Hematopoetic Stem Cell Transplantation On Disease Recurrence: Potential Anti-Leukemic Activity

Blood ◽

10.1182/blood.v122.21.180.180 ◽

2013 ◽

Vol 122 (21) ◽

pp. 180-180 ◽

Cited By ~ 4

Author(s):

Mauricette Michallet ◽

Mohamad Sobh ◽

Stephane Morisset ◽

Helene Labussiere ◽

Marie Y. Detrait ◽

...

Keyword(s):

Stem Cell ◽

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Chelation ◽

Disease Recurrence ◽

Hazard Ratio ◽

Iron Chelators ◽

Myeloid Leukemias

Abstract Iron overload (IO), primarily related to multiple red blood cell transfusions, is a relatively common complication in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Elevated pre-transplant ferritin level, a surrogate marker of iron overload, was demonstrated to be an important cause of mortality and morbidity in patients who have undergone allo-HSCT. Excessive iron accumulation results in tissue damage and organ failure, mainly as a result of the generation of free radicals that cause oxidative damage and organ dysfunction. Iron chelators have been widely used leading to normalisation for ferritine level and lower IO-related complications. As iron has a fundamental role in cell survival affecting pathways involved in DNA synthesis, cell differentiation, and apoptosis, some studies evaluated the anti-proliferative activity of iron chelators in cancer and leukemia patients on disease recurrence. The objective of this study was to determine at a first time the impact of serum ferritin level measured at time of allogeneic HSCT in adult patients with hematological disorders on the different outcomes and to investigate at a second time the role of iron chelation on relapse incidence. We included 158 patients, 100 males and 58 females with a median age of 45 years (18-67) who underwent allo-HSCT between 2002 and 2010. There were 83 acute myeloid leukemias, 10 chronic myeloid leukemias, 11 myelodysplastic syndromes, 7 myeloproliferative disorders, 19 myelomas, 9 non-Hodgkin lymphomas, 6 Hodgkin diseases, 5 aplastic anemias and 3 hemoglobinopathies. Sixty-seven (42%) patients were sex mismatched (F→M:37; M→F:30); for ABO compatibility, 61% were compatible, 18% had minor incompatibility and 21% had major incompatibility. Concerning the HSCT procedures, 60 patients (38%) received peripheral blood stem cell and 98 (62%) received bone marrow from 97 (61%) HLA related donors [matched, n=76; mismatched, n=21], and 61 (39%) HLA unrelated donors [matched, n=36; mismatched, n=25] after myeloablative [n=64, (41%)] or reduced intensity conditioning [n=94, (59%)]. At transplantation, 91 (58%) were in complete remission (CR) or chronic phase [CR1: n=61 (67%); ≥CR2: n=30 (33%)]. The median serum ferritin level at HSCT was 1327 microg./l (26-14136); 31(20%) patients had a level 26-500, 33 (21%) had a level 500-2500, and 94 (59%) >2500. There was no significant correlation between the different ferritin levels, disease kind and status at HSCT. After transplantation, 23 patients received iron chelating agents after a serum ferritin level of 1000 microg/l and stopped when the level decreased below 1000. The cumulative incidence of acute GVHD ≥ II at 3 months was 14% (11-16.5) with 10.5% (8-13) for grade III and 7% (5-9) for grade IV; the 1 year cumulative incidence of limited and extensive chronic GVHD were 4% (2-6) and 12.4% (9-16) respectively. After a median follow-up of 18 months (1-106), the 5 years OS probability was 65% for patients with ferritin level below 500 microg./l, 39% for level between 500 and 2500 microg./l and 28% for level > 2500 micog./l, [Hazard ratio= 3.5 (1.5-8.1), p=0.002]; this was explained by a significant higher TRM in patients with level >2500 [Hazard ratio= 4.3 (1.02-18), p=0.04]. Interestingly, we found in multivariate analysis that patients receiving iron chelators had significantly better OS [5 years OS= 59% vs. 34% for non-chelated patients, Hazard ratio= 0.34 (0.15-0.76), p=0.008], (Figure 1a), and experienced less disease relapse [5 years relapse incidence= 18% vs. 41% for non-chelated patients, Hazard ratio= 0.22 (0.07-0.73), p=0.012], (Figure 1b). In conclusion, we confirmed the negative impact of iron overload on the outcomes allo-HSCT recipients. More importantly, we demonstrated that iron chelators have a positive impact in reducing disease relapse by the possible mechanism of iron deprivation in leukemic cells. This clinical observation needs to be confirmed by prospective randomized trials.Figure 1a: Overall survival probability and b: relapse incidence in patients with or without iron chelationFigure 1. a: Overall survival probability and b: relapse incidence in patients with or without iron chelation Disclosures: Michallet: Novartis: Honoraria, Research Funding. Nicolini:Novartis: Consultancy, Honoraria, Research Funding.

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