Serum ferritin in the diagnosis of cardiac and liver iron overload in thalassaemia patients real-world practice: a multicentre study

Abstract Abstract 3183 Background: The introduction of iron chelation treatment has led to a significant improvement in morbidity and overall survival in patients with transfusion-dependent anemias. Deferasirox is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in both adult and pediatric patients. The efficacy and safety of deferasirox in a variety of transfusion-dependent anemias has been established in numerous Phase II/III clinical trials. Since most patients with transfusion-dependent anemias require lifelong iron chelation therapy, there is a need to assess the long-term safety of deferasirox in both adult and pediatric patients. Aim: To assess the safety profile of deferasirox in patients with transfusional iron overload in a real-world clinical setting. To further investigate the safety profile of deferasirox in patients with congenital erythrocyte disorders and transfusional iron overload, with ferritin levels <4000 ng/ml and without severe cardiac siderosis. Methods: Between July 2009 and September 2010, 85 patients with transfusion-induced iron overload treated with deferasirox as per the approved product labeling were enrolled in the study. These data represent the 24-week planned interim analysis of a 12-month observational study on deferasirox safety profile in the treatment of pediatric and adult patients with transfusion-dependent anemias who were newly-treated with deferasirox. Safety was evaluated through the monitoring and recording of all adverse events and serious adverse events, as well as routine laboratory testing, including hematology, blood chemistry and hepatic function assessments. Results: The population had a median age of 37.6 years (range: 5.3–61.4) and a female to male ratio of 1.3. Beta-thalassemia (67.1%) was the most common transfusion-dependent anemia, followed by thalassemia intermedia requiring periodic transfusions (20.0%) and sickle cell anemia (12.9%). Mean baseline ferritin levels were 1502.1±870.5 (pediatric group: 1480.2±522.8 and adult group: 1503.6±891.4), while 53 out of the 85 patients (62.4%) had serum ferritin level above 1000 ng/ml. Mean baseline liver T2* value was 10.4±9.7 ms; 44.4% of patients demonstrated minimal liver iron deposition (MRI T2* > 6.3 ms), 51.4% had mild to moderate liver iron overload (T2* ≤ 6.3 ms), and 4.2% had severe liver iron overload (T2*<1.4 ms). 54 (63.5%) of patients analysed had been pre-treated with iron chelators and 31 (36.5%) were chelation-naïve. The initial average daily dose of deferasirox was 25.9±4.8 mg/kg, and 70.6% of patients had no dose modification during the 24-week follow-up period. A statistical significant decrease in median serum ferritin levels was observed by Week 24 (mean absolute change from baseline:-214.5 ng/mL; p=0.009) [Figure 1]. No statistically significant changes were observed in creatitine levels, creatinine clearance and transaminases by Week 24 [Figure 1]. 37 ADRs were reported by 17 patients (20%) over the 24-week period. Among the most frequently observed ADRs (>5%) were epigastralgia reported by 7.1% of patients (6/85) and loose stools/diarrhoea by 5.9% of patients (5/85). The majority of ADRs reported (nevents=25; 67.6%) were graded as mild in severity, while 21.6% (nevents=8) were graded as moderate and 10.8% (nevents=4) as severe. Most ADRs (nevents=31; 83.8%) resulted in full recovery by Week 24. The overall incidence of SADRs was as low as 1.2% (in particular one patient experienced severe epigastralgia and upper extremity pain which resulted in her withdrawal from the study after four months of treatment). The all-cause discontinuation rate was 9.4% (8/85), while only two patients (2.4%) discontinued the study therapy due to ADR; 1 patient due to increased transaminase levels and 1 patient due to the aforementioned SADR. Conclusions: These data highlight the safety profile of deferasirox in both adult and pediatric patients; the regular monitoring of serum ferritin levels as well as other iron-overload parameters and transfusion requirements play a major role in determining and optimizing the outcome of iron chelation therapy. Disclosures: Ladis: Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Drossou:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Vini:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Athanasiou-Metaxa:Novartis Hellas S.A.C.I.: Research Funding. Oikonomou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Vlachaki:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Tigka:Novartis Hellas S.A.C.I.: Employment. Tzavelas:Novartis Hellas S.A.C.I.: Employment. Liakopoulou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Adamopoulos:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Kattamis:Novartis Hellas S.A.C.I.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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The Effect of Combination Iron Chelating Agents on Reducing the Severity Grading of Heart and Liver Iron Overload in β-Thalassemia Patients

Iranian Journal of Pediatric Hematology & Oncology ◽

10.18502/ijpho.v9i4.1573 ◽

2019 ◽

Author(s):

Majid Ghanavat ◽

Alireza Fazeli Varzaneh ◽

Nahid Reisi

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Deposition ◽

Liver Iron ◽

Liver Iron Overload ◽

Severity Grading ◽

Group A ◽

Group B

Background: Deferasirox (DFX), Deferoxamine (DFO), and Deferiprone (DFP) are iron chelators that can be used in thalassemic patients with iron overload. Materials and Methods: This clinical trial was performed on 108 thalassemic patients who were randomly divided into group A (n=54) and B (n=54). Group A received combination of DFX and DFP, and group B received DFO and DFP for six months. Serum ferritin level was measured at the beginning of the study, 3, and 6 months after the treatment; The heart and liver iron deposition rates were also measured at the beginning of the study, and 6 months after the treatment in both groups and compared using Magnetic Resonance Imaging T2 plus (MRI T2*). Results: The mean age of patients in group A and B was 17.29±4.3 and 17.89±5.61 years old, respectively. Serum ferritin level significantly reduced after the treatment (Serum ferritin level at baseline, 3, and 6 months after the treatment in Group A: 2476.25±1289.32, 2089.62±1051.64 and 1290.22±724.78 ng/ml, respectively; in Group B: 2044.63±989.82, 1341.30±887.62 and 1229.41±701.22 ng/ml, respectively) (p<0.01, for both groups). MRI T2* heart and liver was also improved at the end of the study in both groups (p<0.01, for both groups). However, the combination of DFO/DFP significantly decreased severity grades of liver iron deposition in comparison to DFX/DFP regimen after six months (p<0.01). Conclusion: The results of the present study indicated that both combination therapies of DFO/DFP and DFX/DFP could improve heart and liver MRI T2*. However, DFO/DFP combination therapy was more effective in reducing the severity grades of liver iron deposition.

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Iron Overload Status in Patients with Non-Transfusion-Dependent Thalassemia in China

Blood ◽

10.1182/blood.v128.22.1287.1287 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1287-1287

Author(s):

Rong rong Liu ◽

Yu mei Huang ◽

Peng Peng ◽

Xiao yun Wei ◽

Yu Lei ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Genetic Disorder ◽

Chinese Patients ◽

Beta Thalassemia ◽

Iron Level ◽

Liver Iron ◽

Liver Iron Overload ◽

Medical University ◽

Hbh Disease

Abstract Background: Non-transfusion-dependent thalassemia (NTDT) is a genetic disorder most commonly including beta-thalassemia intermedia (Beta-TI), HbE/Beta thalassemia (HbE/Beta thalassemia), and hemoglobin H disease (HbH disease). NTDT patients can be at risk of iron overload due to increased intestinal iron absorption triggered by chronic anemia, ineffective erythropoiesis and, possibly, decreased serum hepcidin. Despite NTDT is popular in southern China, there is little data evaluating iron overload in Chinese patients. This study aimed at investigating the occurrence, prevalence and severity of iron overload in Chinese population with NTDT. Methods: We evaluated the serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 158 NTDT patients (83 with HbH disease, 45 with Beta-TI and 30 with HbE/Beta thalassemia) in China. The median age was 22 years old. The main characteristics of these patients along with the main results of the study were summarized in Table 1. Blood samples were obtained for the assessment of hemoglobin (Hb) and serum ferritin (SF) levels. LIC was assessed by using validated R2 magnetic resonance imaging [MRI] (FerriScan®). Cardiac iron level was measured by MRI T2*. Patients were scanned with MRI 1.5 T (Siemens Avanto, Germany). The study was performed at the First Affiliated Hospital of Guangxi Medical University. LIC < 3mg Fe/g dw and cardiac T2* > 20ms was considered normal. Abnormal LIC can be divided into mild: 3-7mg Fe/g dw, moderate: 7-15mg Fe/g dw, severe: >15mg Fe/g dw. All patients or parents/guardians provided their written informed consent to participate in this study. The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Results: The median SF level of 158 NTDT patients was 1,037(27.0-19,704) ng/ ml. LIC was detected in 155 patients (98.1%) and the median LIC value was 8.9(0.6-43) mg Fe/g dw. There were 15 patients (60%) (8 with HbH disease, 5 with Beta-TI and 2 with HbE/Beta thalassemia)<10 years old found liver iron overload. The youngest patient with liver iron overload was 5 years old with 5.6mg Fe/g dw in LIC. Cardiac T2*was assessed in 111 patients (70.2%) and the median cardiac T2* was 32.8(7.5-75.1)ms. The 7 patients (4.4%) (4 with HbH disease and 3 with Beta-TI) had cardiac T2*=<20ms. There was a significant correlation between LIC and SF (r=0.809, p<0.001). No correlation between LIC and Hb, cardiac T2* values can be verified. There was a significant correlation between LIC and age (r=0.497, p<0.001)(Fig 1). The levels of LIC in patients > 30-year old group are significantly higher than those in other groups (Fig 2).The patients with Beta-TI and HbE/Beta thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of HbH disease patients. Conclusions: Chinese NTDT patients have a high prevalence of iron overload. The iron overload in patients with Beta-TI and HbE/Beta thalassemia are more serious than those in HbH disease patients. The age of patient is a risk factor of iron overload in NTDT patient. Patients > 30 years old have a high burden of iron overload. Our data shows that the first assessment of MRI LIC should be performed as early as 5 years old. Disclosures No relevant conflicts of interest to declare.

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Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2017.08.002 ◽

2017 ◽

Vol 66 ◽

pp. 24-30 ◽

Cited By ~ 6

Author(s):

Rungroj Krittayaphong ◽

Vip Viprakasit ◽

Pairash Saiviroonporn ◽

Noppadol Siritanaratkul ◽

Suvipaporn Siripornpitak ◽

...

Keyword(s):

Iron Overload ◽

Multicenter Study ◽

Real World ◽

Real World Data ◽

Liver Iron ◽

World Data ◽

Liver Iron Overload

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Utility of Tissue Elastography in Measuring Liver Iron Overload in Comparison to MRI T2 and Serum Ferritin in Patient with Thalassemia Major

Journal of Clinical and Experimental Hepatology ◽

10.1016/j.jceh.2016.06.141 ◽

2016 ◽

Vol 6 ◽

pp. S85

Author(s):

Kaivan Shah ◽

Nirav Pipaliya ◽

Prabha Sawant

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Thalassemia Major ◽

Liver Iron ◽

Liver Iron Overload ◽

Tissue Elastography

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Clinical-Pathological Features of Non-Transfusion Dependent Thalassemia in Adults — a Single Center Study in Hong Kong

Blood ◽

10.1182/blood-2018-99-113487 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4900-4900

Author(s):

Ka Lok Luke Chan ◽

Vivien W M Mak ◽

Kate F S Leung ◽

Joyce H Y Kwong ◽

Nelson C N Chan ◽

...

Keyword(s):

Hong Kong ◽

Liver Fibrosis ◽

Iron Overload ◽

Serum Ferritin ◽

Transfusion Requirement ◽

Liver Stiffness ◽

Leg Ulcer ◽

Liver Iron ◽

Liver Iron Overload ◽

Hbh Disease

Abstract Introduction: Non-transfusion dependent thalassemia (NTDT) includes HbH disease, β-thalassemia intermedia (β-TI) and HbE/β-thalassemia. The transfusion requirements of patients with NTDT are variable and they are all at risk of developing iron overload and other complications. The prevalent genetic changes in thalassemia are different across geographical territories, accounting largely for the diverse clinical outcomes. The complication profile of NTDT in Southern China is less well studied than other areas. Data on age-related complications is sparse. The present study aims to describe the clinical-pathological features of adult NTDT patients in Hong Kong, and to evaluate the risk factors associated with complications. Method: A single-center observational study was performed during Jan 2017 to Jun 2018. Data collection included review of medical records for demographics; globin genotypes; hepatitis B and C status; transfusion requirement; splenectomy; iron chelation therapy; complications including gallstone disease, hypothyroidism or hypogonadism, diabetes mellitus (DM), extramedullary hematopoiesis (EMH), leg ulcer, venous thrombosis and cerebral ischemia. During the study period, steady state hemoglobin (Hb) and serum ferritin levels in the recent year were obtained; organ iron deposition assessed using liver and cardiac T2* at 1.5T MRI; liver stiffness measured by Fibroscan; and presence of pulmonary arterial hypertension (PAH) evaluated by echocardiography. The disease profile and prevalence of complications were described with descriptive statistics. Factors impacting clinical parameters and development of complication were studied with univariate regressions. Age and sex adjusted β-coefficients or odd ratios were then determined with multivariable regression analysis. Results: A total of 96 Chinese patients were recruited (mean age 50±15 years; 31% patients >60 years; females 66%). There were 63 (65%) patients having deletional HbH disease, 20 (21%) with non-deletional HbH disease (ND-HbHD), and 13 (14%) with β-TI. The mean Hb was 8.9±1.1 g/dL. Transfusion requirement was never in 39 (41%), occasional in 50 (52%), and regular in 7 (7%) patients. Ten (10%) patients were splenectomized. Iron chelation was given to 21 (21%) patients and the median duration of therapy was 3 (range 1-21) years. Respectively 4 (4%) and 2 (2%) patients were hepatitis B and C carriers. The median serum ferritin was 473 [IQR 217-1029] ng/mL. The median liver iron concentration (LIC) estimated by MRI T2* was 3.6 [IQR 1.7-7.1] mg Fe/g with 26% of patients having moderate to severe liver iron overload (≥7.1 Fe mg/g). In the study population, the prevalence of liver fibrosis (liver stiffness ≥7.1kPa) was 26%, gallstones 50%, hypo-thyroidism/-gonadism 8%, DM 16%, EMH 5%, leg ulcer 1%, thrombotic events 2%, cardiac iron overload 1%. No patients had PAH (Table 1). In multivariable regression, advanced age (>60 years) was associated with lower Hb (p=0.03), higher risk of liver fibrosis (p=0.04) and DM (p<0.01). β-TI was associated with higher transfusion requirement (p<0.01), higher serum ferritin (p<0.01) and higher risk of hypo-thyroidism/-gonadism(p=0.01). Both ND-HbHD and β-TI were associated with higher LIC (p<0.01). Patients requiring regular transfusions had higher serum ferritin (p<0.01) and LIC (p<0.01). Occasionally transfused (p=0.01) and female patients (p=0.01) had higher risk of developing gallstones. Splenectomy was associated with higher serum ferritin level (p=0.03). Patients with moderate to severe liver iron overload had increased risk of liver fibrosis (p=0.01) (Table 2). Conclusions: The present study including 1/3 of elderly patients illustrates the heterogeneous clinical features of NTDT in Hong Kong in terms of transfusion requirement and body iron store. HbH disease is the most frequent type of NTDT. Liver iron overload, liver fibrosis, gallstones and DM were the most common complications. Advancing age, β-TI, ND-HbHD were associated with higher risk of developing complications. A low prevalence of EMH, cardiac iron overload, PAH, thrombosis and leg ulcer was observed. Larger prospective study is needed to confirm the prevalence of complications in NTDT in Chinese, which may be different from other ethnic groups, and at the same time to provide more insight to the pathophysiology of NTDT and facilitate establishment of future local management strategies. Disclosures No relevant conflicts of interest to declare.

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