Transfusion-dependent Thalassemia Research Articles

Obesity, liver steatosis and metabolic syndrome: The hidden enemies in transfusion-dependent thalassaemia.

In their paper, the authors quantified liver iron concentration (LIC) and hepatic steatosis (HS) using MRI-T2* technology in transfusion-dependent thalassaemia (TDT) patients and healthy controls and found that the prevalence of HS among patients with TDT was 36.4%. In comparison with healthy controls, the hepatic fat fraction (FF) was significantly higher in the TDT population (p = 0.013). Active hepatitis C virus infection, body mass index (BMI) and LIC were independent predictors of HS. An inverse correlation between hepatic FF and high-density lipoprotein cholesterol (p = 0.042) and a significant association of high glycaemia level (p = 0.037) with higher hepatic FF and a significant relationship (p = 0.026) between HS and higher BMI (though in a 'lean' group of patients) in TDT patients indicated that 'metabolic syndrome' was present in this subset with TDT. The impact of metabolic syndrome on TDT, including cardiac disease unrelated to iron overload, needs further study. Commentary on: Ricchi etal. Liver steatosis in patients with transfusion-dependent thalassaemia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19496.

In brief: Casgevy for beta thalassemia.

Exagamglogene autotemcel (Casgevy – Vertex), a cell-based gene therapy recently approved for treatment of sickle cell disease1, has now been approved by the FDA for treatment of patients ≥12 years old with transfusion-dependent beta thalassemia.

Liver steatosis in patients with transfusion-dependent thalassaemia.

We evaluated the prevalence and the clinical associations of liver steatosis (LS) in patients with transfusion-dependent thalassaemia (TDT). We considered 301 TDT patients (177 females, median age = 40.61 years) enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network, and 25 healthy subjects. Magnetic resonance imaging was used to quantify iron overload and hepatic fat fraction (FF) by T2* technique and cardiac function by cine images. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Hepatic FF was significantly higher in TDT patients than in healthy subjects (median value: 1.48% vs. 0.55%; p = 0.013). In TDT, hepatic FF was not associated with age, gender, serum ferritin levels or liver function parameters, but showed a weak inverse correlation with high-density lipoprotein cholesterol. The 36.4% of TDT patients showed LS (FF >3.7%). Active hepatitis C virus (HCV) infection, increased body mass index and hepatic iron were independent determinants of LS. A hepatic FF >3.53% predicted the presence of an abnormal OGTT. Hepatic FF was not correlated with cardiac iron, biventricular volumes or ejection fractions, but was correlated with left ventricular mass index. In TDT, LS is a frequent finding, associated with iron overload, increased weight and HCV, and conveying an increased risk for the alterations of glucose metabolism.

Serum Zinc and Copper Levels in Children with Thalassemia Major

Background: Thalassemia is a frequent hereditary genetic with different clinical manifestations from mild to severe based on its genetic. Beta thalassemia major is the worse form of this disease caused by decreased or absent beta globin chains of hemoglobin. Regular blood transfusion is the main aim leads to iron overload and deposition of iron in different organs.Objectives: To determine different serum distribution levels and correlation of copper and zinc in transfusion dependent thalassemia patients Material and Methods: This was a descriptive cross-sectional study in which a non-probability convenient sampling technique was used for sample collection. This study was conducted in KPK in a total of 137 patients, who were diagnosed cases of thalassemia major by hemoglobin electrophoresis, enzyme linked immunosorbent assay (ELISA) method and receiving iron and folate therapy. SPSS version 22 was used and Pearson's correlation coefficient was applied. P-value 0.05 was considered significant.Results: In this study mean age was 6.7±3.49 years. 77 (56%) percent children were male while 64 (44%) children were female. Mean hemoglobin (Hb) level was 7.43±1.3 gm/dl. Mean SGPT score was 26.28 ± 7.51. Mean blood urea was 21.10 ± 8.49 mmol/l while mean serum creatinine level was 0.56 ± 0.26 mg/dl. Mean serum zinc level was 13.36 ± 11.12mg/dl while mean serum copper level was 1.21± 0.60 mg/dl and mean serum ferritin level was 6682 ± 533 Ug/l.Conclusion: This study showed hypozincemia in thalassemia major patients, but copper deficit was not present. There was no substantial variance between serum ferritin level and mean serum concentration of zinc and copper in this study. Ancillary assessments in this respect is recommended. Keywords: Copper, Thalassemia, Zinc

Good engraftment after reduced intensity targeted busulfan-based conditioning and matched related donor hematopoietic cell transplantation in hemoglobinopathies.

Hematopoietic cell transplantation (HCT) is an established curative therapy for transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). The latest American Society of Hematology guidelines recommend myeloablative preparative regimen in patients under 18years of age. The objective was to demonstrate safety and efficacy of a reduced intensity conditioning (RIC) regimen including high-dose fludarabine, anti-thymocyte globulin, and targeted busulfan as a single alkylator to sub-myeloablative exposures. Between 2012 and 2021, 11 patients with SCD and five patients with TDT and matched related donor (MRD) HCT were included. The median age at transplantation was 8.3years (range: 3.7-18.8years). The median administered busulfan AUC was 67.4mg/L×h (range: 60.7-80mg/L×h). Overall survival was 93.8% and event-free survival 87.5% with one engrafted SCD patient with pre-existing moyamoya disease succumbing after drainage of a subdural hematoma. One SCD patient developed a secondary graft failure and was treated with a second HCT. Myeloid chimerism was full in all other patients with a median follow-up time of 4.1years (range: 2.0-11.1years), whereas T-cell donor chimerism was frequently mixed. This RIC conditioning followed by MRD HCT is sufficiently myeloablative to cure pediatric patients with hemoglobinopathies without the need for additional total body irradiation or thiotepa.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand

Background Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. Objectives To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. Patients and methods We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. Results A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39–9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20–7.92, p < 0.001) were independently associated with poorer survival. Conclusions Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (β-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of β-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 β-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 μmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 μmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in β-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia

To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

The relationship between increased iron load and respiratory function tests in patients diagnosed with transfusion dependent thalassemia

Aims: Thalassaemia syndromes are the most common single gene disorders affecting more than 200 million people worldwide. Beta thalassaemia (BT) is the most common cause of transfusion-dependent thalassaemia (TDT). It has been reported in studies that iron accumulation occurs in the lungs, especially in the alveolo-capillary membrane, and the frequency of parenchymal disease increases in patients receiving frequent blood transfusions. In our study, we aimed to investigate whether there is a correlation between iron overload and pulmonary function in patients with TDT.&#x0D; Methods: The study included 61 patients aged between 18 and 45 years with a diagnosis of TDT who were followed up in the hematology clinic of our tertiary care center between 2018 and 2023. Based on spirometry measurements, the pattern of respiratory impairment was defined and correlated with serum ferritin levels. &#x0D; Results: The mean age of the 61 patients included in the study was 24.83±6.02 years and 33 were female and 28 were male. The mean ferritin value was 3150.88±2553.51 ng/ml. The annual number of transfusions was 15.39±1.90. According to the PFT results, mean FVC % value was 81.59±9.28, mean FEV1 % value was 82.11±7.6, mean FEV1/FVC % value was 102.55±7.63. Mean ferritin values were found to be significantly higher in patients diagnosed with TDT with restrictive lung pattern (p=0.004). &#x0D; Conclusion: Our study showed that high ferritin levels are related to increased restrictive lung disease in the adult age group.

Analysis of Hepcidin and Interleukin-6 Levels among Transfusion-Dependent Thalassemia Patients With and Without Alloimmunization/Autoimmunization

Analysis of Hepcidin and Interleukin-6 Levels among Transfusion-Dependent Thalassemia Patients With and Without Alloimmunization/Autoimmunization

A Cross-Sectional, Multicentric, Disease-Specific, Health-Related Quality of Life Study in Greek Transfusion Dependent Thalassemia Patients.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). Sixty-three (73%) patients had pancreatic IO (R2*>38Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18±3months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Haemoglobin lepore and beta thalassaemia traits – Prenatal testing by both sequence analysis and MLPA for HBB gene: A case report

Hb Lepore is a fusion globin protein made of fused chains of delta and beta globin. It is a deletion haemoglobinopathy. In homozygote form, it is similar to transfusion dependent beta thalassaemia major, and in the heterozygous form, it causes mild microcytic hypochromic anaemia. In this case report, the couple has heterozygous Hb Lepore and heterozygous beta thalassaemia, with a pregnancy of 15weeks gestation. Prenatal testing by amniocentesis and HBB gene analysis for the fetus was done by sequencing and MLPA to detect the different types of mutations present in the parents. This case report reveals the importance of MLPA to be done along with sanger sequencing, to detect all types of mutations in the HBB gene.

Correlation of anthropometric measurements with pretransfusion haemoglobin in transfusion dependent thalassemia major children

Background: The etio-pathogenesis of growth failure in transfusion dependent thalassemia major (TDTM) children is mainly because of chronic anemia, iron overload and endocrine complications. Aim was to determine the association between anthropometric measurements with pre-transfusion haemoglobin in TDTM children. Methods: Present cross-sectional study included total 55 children between 5-18 years of age who were diagnosed as TDTM. Mean pre transfusion hemoglobin of last 1 year was obtained from previous medical records. Anthropometric measurements like weight in kg and height in cm measured while body mass index (BMI) was calculated using standard formula in each patient. Weight for age, height for age, and BMI were plotted on WHO 2006 and Indian academy of paediatrics 2015 combined growth charts in terms of percentile. Data was analysed statistically. Results: Total 55 children of TDTM between 5-18 years of age were studied. The mean age was 10.42(4.07) years. The mean weight (kg), height (cm) and BMI was 23.76 (7.5), 123.94 (18.13) and 15.24 (1.76) respectively. Fifty-one (92.73%) children were having BMI less than 3rd centile (Underweight). Forty (93.02%) and 11 (91.66%) children between age group of 5-10 years and more than 10 years were underweight and was statistically significant (p&lt;0.05). Total 50 (94.33%) children were having mean pre transfusion hemoglobin below 9 gm/dl who were underweight which was statistically significant. Conclusions: Low pre-transfusion hemoglobin is one of the risk factors for growth failure in children with TDTM and it should be maintained above 9 gm/dl may for normal growth in children with TDTM.

Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression

We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1–2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 107/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.

Awareness and practices regarding thalassemia among parents of transfusion dependent beta thalassemia patients registered with Hamza Foundation Peshawar, Pakistan

Thalassemia, a pervasive and chronic condition that impacts an estimated 200 million people worldwide, is predominantly caused by the beta-thalassemia gene, which is found in approximately 3% of the global population. The purpose of this research, which was carried out from June to December 2022 at the Haemophilia Hospital of the Hamza Foundation Welfare Thalassemia, was to evaluate the knowledge and behaviours of guardians of transfusion-dependent beta-thalassemia patients who were registered with the foundation. The findings of the research, which utilised non-probability convenience sampling to select 150 parents, indicated that 38.7% of the parents surveyed were cognisant of thalassemia, whereas permanent treatment was conspicuously unknown to them. Furthermore, it is noteworthy that a substantial proportion (94%) of parents readily shared food, underscoring the criticality of implementing educational and awareness campaigns targeting not only parents but the broader populace in order to rectify the lack of understanding regarding thalassemia. The fact that genetic counselling was availed of by a minuscule proportion (13.3%) of parents underscores a possible avenue for enhancement in comprehensive care approaches.

Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis

BackgroundThalassemia is a genetic hemoglobinopathy in which a defective globin chain can cause transfusion-dependent anemia and other complications. As genotype interactions lead to variations in the clinical course among patients with thalassemia, clinical factors may help predict survival in the types of thalassemia complicated by gene interactions.AimThis study aimed to determine the clinical factors associated with survival in patients with thalassemia. We retrospectively reviewed the medical records of patients with thalassemia older than 15 years between 2002 and 2020 that were available at the Rajavithi Hospital. Data on the clinical parameters, laboratory tests, treatments, and survival status were collected and analyzed.ResultsOf the 478 thalassemia patients included, 68.8% were women, and the mean age was 41 ± 17 years. The most common type of thalassemia was β-thalassemia (53.3%). Male sex, low body mass index, the thalassemia type, comorbidities, low hemoglobin level, high ferritin level, and regular blood transfusion were significantly associated with short-term survival. However, only the thalassemia type (β-thalassemia, p = 0.048) and the co-inheritance of the α- and β-thalassemia genotypes (p = 0.03) were independently associated with death. The overall survival rates among patients with α-thalassemia, β-thalassemia, and co-inheritance of the α- and β-thalassemia genotypes were 98.1%, 90.6%, and 75.0%, respectively. The death rate was 6.3%, and the most common cause of death was infection.ConclusionThe thalassemia genotype was a predictive factor of survival, and co-inheritance of the α- and β-thalassemia genotypes results in a shorter-term survival compared with other types, especially transfusion-dependent thalassemia. These results can be applied in clinical settings to predict and possibly extend the life expectancy of patients with thalassemia.

Audiologic and vestibular assessment in children and adolescents with transfusion dependent beta thalassemia major: The era of deferasirox film coated tablet

BackgroundHearing impairment has frequently been described in β-thalassemia patients with a significant impact on the patients’ quality of life. Most studies provided evidence of deferoxamine (DFO) dose-related ototoxicity, however, the data is scarce regarding deferasirox (DFX) as a sole iron chelator. AimWe aimed to assess the prevalence and risk factors of sensorineural hearing loss (SNHL) and vestibular dysfunction in regularly transfused β-thalassemia patients who had been treated with DFX film coated tablets. MethodsWe conducted a case control study on 57 transfusion dependent β-thalassemia patients with a mean age of 15.3 years who received DFX FCT as monotherapy for at least one consecutive year, and 57 healthy age and sex-matching controls. Comprehensive audiological evaluations using pure tone audiometry (PTA) and transient evoked otoacoustic emission (TEOAE) as well as vestibular evaluation using Video-nystagmography (VNG) were done. ResultsSNHL was identified in 12 patients (21.1 %) using PTA and a statistically significant difference was detected between controls and patients at 6 KHz and 12 KHz frequencies. A higher incidence of SNHL was detected using TEOAE, 22 patients (43.1 %) failed to pass TEOAE, with a statistically significant decrease in the signal at frequencies 1, 4 KHz bilaterally and at frequencies 1.5, 2 KHz in the right ear compared to controls. Canal paresis was detected in 21 (36.8 %) of thalassemic children using bithermal caloric test with significantly more unilateral weakness than control children (P = 0.008). We found no significant correlation between audio-vestibular dysfunction and age, sex, serum ferritin, frequency of blood transfusion and dose of DFX FCT in thalassemic children. ConclusionWe conclude that the incidence of SNHL and vestibular dysfunction was high among transfusion dependent β-thalassemia patients. Therefore, we recommend performing pre-treatment baseline audio-vestibular assessment and yearly audio-vestibular monitoring to early detect high risk patients and initiate timely management to prevent permanent damage.

Two risk factors for hypozincemia in diabetic β-thalassemia patients: Hepatitis C and deferasirox.

Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and β-Thalassemia patients. We aimed to evaluate the level of serum zinc in β-thalassemia patients with DM and a risk assessment for hypozincemia. The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 μg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020. Of 64 diabetic β-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 μg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In β-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7. In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic β-thalassemia cases. However, upward bias should be taken into consideration.

Efficacy and Safety of a Dispersible Tablet of GPO-Deferasirox Monotherapy among Children with Transfusion-Dependent Thalassemia and Iron Overload

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/β-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia.