scholarly journals Iron Overload in Transfusion-Dependent Indonesian Thalassemic Patients

Anemia ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Pandji Irani Fianza ◽  
Anita Rahmawati ◽  
Sri Hudaya Widihastha ◽  
Shofura Afifah ◽  
Mohammad Ghozali ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Organ Damage ◽  
Cardiac Damage ◽  
Cardiac Siderosis ◽  
Magnetic Resonance Imaging Mri ◽  
Chain Synthesis ◽  
Globin Chain Synthesis ◽  
T2 Mri

Thalassemia is a genetic disease caused by disruption of globin chain synthesis leading to severe anemia and thus regular blood transfusion is necessary. However, there have been known transfusions-related consequences, including iron overload and multi-organ damage. The aims of this study were to evaluate liver and cardiac function in youth and adult transfusion-dependent Indonesian thalassemic patients and to assess its correlation with serum ferritin levels, as well as T2 ∗ magnetic resonance imaging (MRI). Transfusion-dependent thalassemic (TDT) outpatients (n = 66; mean age, 21.5 ± 7.2 years) were carried out for the complete assessment consisting of blood test including liver enzyme and serum ferritin, followed by electrocardiography (ECG) and echocardiography. Subjects were also divided by serum ferritin levels into three groups: < 2500 ng/mL, 2500–5000 ng/mL, and >5000 ng/mL. Additionally, subgroup analysis in patients with T2∗ MRI assessment was conducted. In terms of age of first blood transfusion, subjects with ferritin >5000 ng/mL were the youngest among others. The alanine aminotransferase (ALT) levels in group with serum ferritin >5000 ng/mL were significantly higher than those of the group with serum ferritin <2500 ng/mL. Additionally, youth and adult TDT patients whose serum ferritin >5000 ng/mL had significantly lower tricuspid annular plane systolic excursion (TAPSE) when compared with those who had serum ferritin <2500 ng/mL. Similarly, TAPSE in patients with moderate cardiac siderosis based on cardiac T2∗ MRI was significantly lower than those without cardiac siderosis. There was significant, but only moderate correlation between serum ferritin and cardiac T2∗ MRI. Based on these findings, it is important to routinely monitor iron accumulation-related complications, including liver and cardiac damage in youth and adult TDT patients.

scholarly journals Liver Enzymes in Children with beta-Thalassemia Major: Correlation with Iron Overload and Viral Hepatitis

2015 ◽  
Vol 3 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Khaled M. Salama ◽  
Ola M. Ibrahim ◽  
Ahmed M. Kaddah ◽  
Samia Boseila ◽  
Leila Abu Ismail ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Iron Overload ◽  
Viral Hepatitis ◽  
Serum Ferritin ◽  
Liver Enzymes ◽  
Transferrin Saturation ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Elevated Liver Enzymes ◽  
Hcv Antibody

BACKGROUND: Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST).AIM: Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes.PATIENTS AND METHODS: Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients.RESULTS: Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group.CONCLUSION: Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload.

Assessment of Iron Overload in a Cohort of Sri Lankan Patients with Transfusion Dependent Beta Thalassaemia and its Correlation with Pathogenic Variants in HBB, HFE, SLC40A1, and TFR2 Genes

2021 ◽  
Author(s):  
Ruwangi Dissanayake ◽  
Nayana Samarasinghe ◽  
Samantha Waidyanatha ◽  
Sajeewani Pathirana ◽  
Vajira HW Dissanayake ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Sri Lankan ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
The Mean ◽  
One Year ◽  
Next Generation Sequencing Ngs ◽  
T2 Mri ◽  
Generation Sequencing

Abstract Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

scholarly journals Serum Ferritin Versus T2*Mri For Estimation Of Iron Overload In Children Treated For Hematological Malignancies

2018 ◽  
Vol 3 (3) ◽  
pp. S6
Author(s):  
Vinay Munikoty ◽  
Deepak Bansal ◽  
Kushaljit Singh Sodhi ◽  
Anmol Bhatia ◽  
Prateek Bhatia ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Hematological Malignancies ◽  
T2 Mri

Non-Invasive Assessment of Pancreatic Iron Stores by Magnetic Resonance Imaging (MRI) in β-Thalassemic Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4052-4052
Author(s):  
Reijane Alves De Assis ◽  
Andreza Alice Feitosa Ribeiro ◽  
Alexandre Henrique C Parma ◽  
Laércio Alberto Rosemberg ◽  
Cesar Higa Nomura ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Myocardial Iron ◽  
Moderate Correlation ◽  
Transfusion Therapy ◽  
Iron Stores ◽  
Non Invasive ◽  
Cardiac Siderosis ◽  
Liver And Pancreas ◽  
Invasive Method

Abstract Abstract 4052 Poster Board III-987 Background Frequent transfusions of red blood cells are considered standard therapy for patients with β-thalassemia. However, this can lead to transfusional iron overload and subsequent end-organ damage with decrease in life-expectancy. Ferritin is the most widely available non-invasive method for assessing iron stores and iron overload in chronically transfused patients. However, it can also be elevated in inflammatory conditions. MRI has been proposed as a non-invasive method for detection and quantification of iron stores in specific organs. Most studies utilizing MRI for detection of iron overload have focused on the heart and liver, and it is unknown if MRI could satisfactory detect iron overload in other potentially involved organs such as pancreas. Aims To evaluate and correlate the level of iron accumulation in different organs and serum ferritin concentrations for 6 months before imaging studies in patients with β-thalassemia receiving chronic transfusion therapy. Methods MRI was used to asses iron content in three different organs (heart, liver, and pancreas) in patients with a diagnosis of β-thalassemia. Validation of the MRI technique was done by determining liver iron concentration (LIC) from 11 liver biopsies. LIC was determined by atomic absorption spectrometry and was correlated with liver T2* measurement obtained with MRI. There was a significant, curvilinear, inverse correlation between liver T2* MRI measurements and the LIC by Pearson′s method (r =-0.878, p=0.001). We used Pearson′s coefficient of correlation to assess association between T2* measurements among different organs (heart, liver and pancreas) and between organs and serum ferritin levels. Results We evaluated 115 patients with a diagnosis of β-thalassemia that were receiving chronic transfusion therapy. Mean age was 21,25 years (range 7-54 years) and 43% were male. Mean T2* value in the liver was 3.91 ± 3.95 ms, indicating significant liver siderosis (T2*<6.3ms) in most patients (92.1%). Mean value of myocardial T2* was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2*<20ms) was 36%. Additionaly, 19% of the patients (22/115) had severe cardiac siderosis (T2* <10ms). Mean T2* value in pancreas was 11.12 ± 11.20 ms, and pancreatic iron deposition (T2* < 21ms) was found in 83.5% of patients. There was no significant correlation between liver and pancreas iron overload (r =0.249), and liver and myocardial iron overload (r =0.149). There was a moderate correlation among pancreas and myocardial iron overload (r =0.546; p=0.001). Mean serum ferritin level was 2,676.5 +/- 2,051.7 ng/mL (range 59-12,362 ng/mL). There was no significant correlation among ferritin serum level and liver, heart and pancreas T2* values (r =-0.397; r =-0.220; r =-0.295). Conclusion Iron overload of liver, heart and pancreas, measured by MRI T2*, could not be predicted by ferritin levels in patients with β-thalassemia. Pancreatic iron overload can be measured by MRI, but we could not predict pancreatic hemosiderosis by detection of iron overload in others organs (except for a moderate correlation among pancreas and heart iron overload). Given that direct calibration of MRI with pancreas biopsies is not possible, further studies are necessary to validate this technique. Disclosures: No relevant conflicts of interest to declare.

Serum Ferritin and Cardiac/Liver Magnetic Resonance Imaging In Evaluating Iron Overload for Patients with Bone Marrow Failure Conditions Undergoing Non-Myeloablative HSCT

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1331-1331
Author(s):  
Victoria J Tindell ◽  
Victoria T Potter ◽  
Rachel Kesse-Adu ◽  
Laura Reiff-Zall ◽  
Aloysius Y Ho ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Bone Marrow Failure ◽  
Acute Phase Reactant ◽  
Hepatic Iron ◽  
Red Cell ◽  
Resonance Imaging ◽  
Phase Reactant ◽  
The Impact ◽  
T2 Mri

Abstract Abstract 1331 Several groups have identified iron overload, in terms of raised pre-transplant serum ferritin levels, as an independent adverse prognostic factor for patients undergoing myeloablative HSCT. While serum ferritin has been used as a common marker in clinical studies to evaluate the impact of iron overload following allogeneic transplantation, there are limitations to its use with it being an acute phase reactant, as well as its lack of specificity for predicting end-organ toxicities. Patients undergoing HSCT for bone marrow failure (BMF) syndromes usually have a significant red cell transfusion history, and although the majority of these patients receive non-myeloablative HSCT regimens, it is unclear as to the impact of iron overload in these patients on subsequent transplant outcomes. In order to address these questions, we performed a prospective study evaluating the pre-transplant serum ferritin together with concurrent T2* cardiac magnetic resonance imaging (MRI) and R2 liver MRI in 18 patients with BMF syndromes undergoing allogeneic HSCT. The diagnosis of the patients included MDS (RCMD/hypoplastic MDS) =10, acquired aplastic anaemia =7, fanconi anaemia =1. The median age of the patients at transplantation was 42 years, and all patients received a T-cell depleted non-myeloablative HSCT. All patients were transfusion dependent pre-HSCT, with a median number of red cell transfusions of 45 (range: 8–115). Pre-HSCT ferritin was performed within 2 weeks of HSCT, and the results were correlated with albumin and C-reactive protein to reduce the impact of ferritin as an acute phase reactant. T2* and R2 MRI were similarly performed within 2 weeks of HSCT. The median pre-HSCT ferritin was significantly raised at 2119 ug/l(range: 559–12235). In contrast, the T2* cardiac MRI was normal for all but one patient who had evidence of mild cardiac iron overload. All patients had a corresponding cardiac echocardiogram performed with an ejection fraction within normal limits. For the liver T2* MRI, 7 patients had evidence of none or mild hepatic iron overload, while 11 patients had moderate to severe iron overload. There was no correlation between pre-HSCT transfusion burden and serum ferritin levels. Furthermore, there was no correlation between either the transfusion burden or serum ferritin, and the T2*MRI readings. In terms of HSCT outcome, the median time to neutrophil engraftment was 14 days. 2 patients had primary graft failure and only 1 patient died within 100 days due to an intra-cerebral haemorrhage. No patients had any clinical features of hepatic veno-occlusive disease (VOD), and 5 patients had evidence of grade I-II acute grade versus-host-disease. Data were also collected on the incidence of bacterial, fungal and viral infections post-HSCT for the cohort. There was however no significant association between transfusion burden, serum ferritin or T2* imaging and any of the HSCT outcomes (engraftment/day 100 TRM, GvHD, VOD or infections). In the context of heavily transfused BMF patients receiving allogeneic HSCT, serum ferritin does not correlate with end-organ deposition of iron. Despite the high transfusion burden in our cohort of patients, cardiac deposition of iron appears minimal while hepatic iron deposition is significant in a large proportion of patients. Reassuringly, a raised iron overload by either of the above mentioned parameters had no effect on HSCT outcomes. Our findings highlight the limitations of using serum ferritin as a marker of iron overload pre-HSCT. The role of active pre-HSCT chelation of BMF patients receiving non-myeloablative HSCT regimens remains unclear, and further studies are warranted. Disclosures: No relevant conflicts of interest to declare.

Transfusional Iron Overload In An Adult Sickle Cell Disease Population: Epidemiology, Prevalence, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1005-1005 ◽  
Author(s):  
James Son ◽  
Hongyan Xu ◽  
Nadine J Barrett ◽  
Leigh G Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Organ Damage ◽  
Morbidity And Mortality ◽  
Genotype Distribution ◽  
Cell Disease ◽  
The Mean

Abstract Transfusional iron (Fe) overload remains a significant problem among patients with chronic, transfusion dependent anemias, especially in transfusion dependent ß-thalassemia (Thal) syndromes. If not treated vigorously with chelation, Fe overload in Thal is associated with significant organ damage, especially with chronic liver disease and cardiac abnormalities which can contribute to morbidity and mortality. In recent decades, the significance of Fe overload in sickle cell disease (SCD) has also been recognized especially among pediatric patients on chronic transfusion regimens predominantly for primary and secondary prevention of stroke. The prevalence and significance of this problem among adult SCD patients is less clear, although it is widely believed that episodic, mostly unnecessary transfusion practices play a more prominent role in this patient population. There have been reports of an association between iron overload and increased morbidity and mortality among adult SCD patients; it has also been speculated that the chronic inflammatory state that exists in SCD affords some degree of protection against severe organ damage through upregulation of hepcidin and sequestration of Fe in these patients. We performed a retrospective review of 635 adult SCD patients followed at our Center to define and ascertain the epidemiology, prevalence, etiology, and clinical correlates of transfusional Fe overload. Fe overload was defined as two consecutive serum ferritin values of > 1000 ng/ml. 80 patients (12.6%) met this criterion. Of these, 38 were male and 42 were female. Genotype distribution was: 73 SS, 3 S-β+ thal, 2 S-β0 thal and 2 SC. The mean age was 35.9 (range 18-69). Out of the 80 patients with transfusional Fe overload, 24 (30%) were/had been on a chronic transfusion regimen (23 for secondary or primary stroke prevention and one for childhood cardiomyopathy). Seventy percent of the patients (n=56) developed Fe overload from episodic transfusions predominantly performed at outlying community hospitals. The mean highest ferritin value was 4991 ng/ml (range 1,052-16,500). There was no correlation between ferritin levels and the number of hospitalizations or painful episodes (p=0.9). Thirty seven patients (46.2%) had a history of chelation therapy (with desferoxamine, deferasirox, or both). In 25 patients who have been on deferasirox for a period of 6 months or more, serum ferritin levels decreased from 4452.3 to 3876.6 ng/ml (p=0.3239). Our retrospective study shows that transfusional Fe overload is not rare among adults with SCD and develops predominantly as a result of episodic blood transfusions. This underscores the importance of the development and dissemination of evidence based guidelines, especially for episodic transfusions in SCD. A careful study of the extent and degree of organ damage associated with transfusional Fe overload in SCD and why less than half (46.2%) of patients are exposed to chelation therapy needs to be done. These studies should include liver iron concentration (LIC), cardiac iron and liver histology, when indicated, in parallel with serum hepcidin levels. The fact that the reduction in serum ferritin levels with deferasirox did not reach statistical significance in this cohort can be explained by the relatively small number of patients as well as by the short period (6 months) of exposure to chelation therapy. Disclosures: No relevant conflicts of interest to declare.

Why Are Hemoglobin F Levels Increased in HbE/β Thalassemia?

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3199-3204 ◽  
Author(s):  
D.C. Rees ◽  
J.B. Porter ◽  
J.B. Clegg ◽  
D.J. Weatherall
Keyword(s):  
Blood Transfusion ◽  
Sequential Data ◽  
Ineffective Erythropoiesis ◽  
Hemoglobin F ◽  
Hemoglobin E ◽  
F Cells ◽  
Before And After ◽  
Chain Synthesis ◽  
Globin Chain Synthesis ◽  
Marrow Expansion

To try to further define the mechanisms that increase the levels of hemoglobin F (HbF) in the blood of patients with severe forms of β thalassemia, we have studied two comparable populations of hemoglobin E (HbE)/β thalassemics, one regularly transfused and one receiving only occasional blood transfusions. Regular transfusion was associated with a significant decrease in soluble transferrin receptor and erythropoietin levels. Globin chain synthesis studies also show a highly significant decrease in HbF synthesis relative to HbE in the transfused patients. This effect was confirmed by sequential data on one patient, studied before and after the commencement of regular blood transfusion; blood transfusion was followed by a marked increase in the /γ, βE/γ, and HbE/HbF ratios. These data suggest that the high HbF levels in HbE/β thalassemia, and other β thalassemia syndromes, result from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with ineffective erythropoiesis giving a survival advantage to F cells. This study also suggests that alteration in blood transfusion regimes must be taken into account when interpreting changes in HbF levels seen in trials of HbF-promoting drugs.

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

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.

scholarly journals Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis – The Value of T2* MRI

2020 ◽  
Vol 13 (2) ◽  
pp. 712-715
Author(s):  
Mustafa A. Al-Tikrity ◽  
Mohamed A. Yassin
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Ferritin Level ◽  
Hereditary Hemochromatosis ◽  
Iron Concentration ◽  
Hfe Gene ◽  
Liver Iron Concentration ◽  
C282y Mutation ◽  
Liver Iron ◽  
T2 Mri

Primary hemochromatosis is an inherited disorder, and the homeostatic iron regulator (HFE) gene C282Y mutation is a common cause of hemochromatosis in Europe. We are reporting a case of a 56-year-old female known to have hemochromatosis with the HFE gene C282Y mutation with a serum ferritin level of 482 μg/L who underwent heart and liver T2* MRI which showed no evidence of iron overload – neither in the heart nor in the liver. This indicates that there is a discrepancy between serum ferritin and liver iron concentration by MRI and the superiority of T2* MRI in diagnosis and follow-up of iron overload in patients with hereditary hemochromatosis.

Phlebotomy and Hydroxyurea for Non-Transfusion Dependent Iron Overload in Beta-Thalassemia Intermedia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4031-4031
Author(s):  
Oscar Boutros Lahoud ◽  
Velta Willis ◽  
William B. Solomon
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelating Agents ◽  
Iron Deposition ◽  
Beta Thalassemia ◽  
Thalassemia Intermedia ◽  
Ineffective Erythropoiesis ◽  
Clinically Significant ◽  
Iron Chelating Agents ◽  
T2 Mri

Abstract Background: Patients with beta-thalassemia intermedia are at increased risk of developing clinically relevant iron overload independent of blood transfusions, which can result in serious sequelae, including liver, myocardial and endocrine dysfunction. This is thought to be modulated by downregulation of hepcidin and upregulation of ferroportin1. Standard of care in these patients has essentially consisted of iron-chelating agents such as deferasirox, presumably based on the hypothesis that phlebotomy would worsen clinical anemia and potentially exacerbate further ineffective erythropoeisis2. We present the cases of two patients with non-transfusion dependent iron overload secondary to beta-thalassemia intermedia, who were treated with serial phlebotomies as well as hydroxyurea. Case #1: Patient A was heterozygous for the Gln39X beta zero thalassemic allele as well as heterozygous for the H63D HFE-1 allele, and presented with a serum ferritin of 1928 ng/ml. T2* MRI of liver and myocardium demonstrated mild iron deposition in the liver and none in the heart. During a period of 18 months Patient A received serial phlebotomies and hydroxyurea 500 mg daily with decrease in serum ferritin to 770 ng/ml with no change in her baseline Hb and an increase in Hb F from 7% to 15%. Repeat T2*MRI of the liver and myocardium demonstrated no clinically significant iron deposition. Patient A continues to be phlebotomized every one to two months. Case #2: Patient B was heterozygous for the Gln39X beta zero allele with no mutant HFE-1 alleles, and presented with a serum ferritin of 1230 ng/ml. T2* MRI of the liver and myocardium demonstrated iron deposition in the liver and none in the heart. Over a period of twelve months patient B received serial phlebotomies and hydroxyurea 500 mg daily with decrease in his serum ferritin to 450 ng/mL, with no change in baseline Hb and no increase in Hb F. Repeat T2* MRI demonstrated no cardiac iron overload and slight improvement in the liver T2* relaxation time. Patient B continues to be phlebotomized every one to two months. Discussion: We presented two cases of non-transfusion dependent iron overload secondary to beta thalassemia intermedia managed with the combination of phlebotomy and low dose hydroxyurea, which resulted in clinically significant decrease in serum ferritin. In both patients the decrease in serum ferritin averaged ~65 ng/ml/month. As a reference, the higher dose regimen of deferasirox 10 mg/kg/d has a reported average decrease in serum ferritin of around 222 ng/mL/year, corresponding to an estimated 18.5 ng/mL/month2. There was no change in either patient’s Hb/Hct or markers of ineffective erythropoiesis such as LDH, indirect bilirubin and reticulocyte count. This could be due to a somewhat protective effect from hydroxyurea, which may decrease unbound alpha-globin chains, thereby permitting phlebotomy while maintaining adequate counts. Conclusion: These two cases suggest that in some non-transfusion dependent patients, the combination of phlebotomy and hydroxyurea may be an appropriate first-line treatment of iron overload due to beta-thalassemia. It appears to potentially offer enhanced efficacy with presumably less toxicity than standard iron-chelating agents in selected patients. Further investigation is needed to determine the specific population that would benefit most from this combination. The optimal treatment modality/combination in those patients has yet to be determined. Additional studies about treatment effect on iron-regulatory pathways are warranted. References: (1) Gardenghi S, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood 2007: 109(11):5027-5035. (2) Taher AT, et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood 2012; 120(5): 970-977. Disclosures No relevant conflicts of interest to declare.

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