Comparison of Visual Evoked Potential in Thalassemia Patients Receiving Iron Chelation Therapy

Patients of thalassemia require iron chelation therapy for the treatment of iron overload in the form of desferrioxamine (DFO), combination of DFO and deferiprone and oral deferiprone only. One of the side effects of DFO is ocular toxicity. Present study was conducted to elicit the subclinical effects of DFO on visual pathways by doing Visual Evoked Potential (VEP). Forty five patients of thalassemia major were divided into three groups (I, II &III) based on their iron chelation therapy as desferrioxamine, combination of desferrioxamine& deferiprone and only deferiprone respectively. VEP was recorded in each group and comparison was done. In VEP P100 was significantly prolonged in the group of thalassemia patients receiving DFO and combination of DFO and deferiprone suggesting vulnerability to ocular toxicity of DFO. We can suggest that in patients receiving chronic DFO therapy, VEPs may be considered to monitor the toxic effects of DFO on visual system. Keywords: Thalassemia, iron chelation, visual evoked potential.

329 Heart failure predictive value of the electric risk score in patients suffering from thalassemia major

Aims Complications associated with iron accumulation were highly recurrent in thalassemia patients, who underwent frequent blood transfusions, in particular hemosiderotic cardiomyopathy which could lead to heart failure and arrhythmias. Nowadays, the better iron chelation therapy has improved cardiovascular morbidity in these patients; nevertheless, mild impairment should be seek for and eventually treated. The objective of our study was to evaluate the possibility of using early electrocardiographic markers of myocardial damage and predictors of mortality, such as the Electric Risk Score (ERS). Methods and results 73 patients with thalassemia major were enrolled in this study, which were divided into two groups, with 45 years old as cut off. Anamnestic, clinical, electrocardiographic, and echocardiographic data were collected. From ECG, ERS was obtained. over 45 yrs-old group of pts, in addition to a predictable increase in the prevalence of traditional cardiovascular risk factors and drug intake, an alteration of the QRS-T angle (14[30] vs. −4[28], p value: <0.0001) and an increased prevalence of left ventricular hypertrophy (2.88 ± 0.86 vs. 2.40 ± 0.57 p value: <0.05) were found. In patients taking drugs with possible interactions with the ventricular repolarization phase, there is a slight increase in the QT interval, left ventricular hypertrophy and a reduction in Tpeak-Tend (Table 1). Electrocardiographic values in groups of patients with different age groups who are taking therapies that can affect QT. The echocardiogram revealed an increase in the end-diastolic diameter of the right ventricle (26 ± 3 vs. 28 ± 3 mm, P-value: 0.05) in the group of patients over the age of 45, a decrease in the acceleration time of the pulmonary systolic flow (138 ± 25 vs. 125 ± 13 ms, P-value: 0.04) and TAPSE (25 ± 3 vs. 22 ± 4 mm, P-value: 0.002). Conclusions From the data in our study it emerged that an appropriate iron-chelation therapy is able to effectively counteract the hemosiderotic cardiomyopathy of thalassemic patients so as to detect electro- and echocardiographic anomalies only in patients of more advanced age, a result that we think both the consequence, not so much of iron overload, but of an increase in the prevalence of age- and gender-related cardiovascular risk factors. The initial changes in cardiac electromechanics, which can be assessed with the aforementioned methods, we believe, can become a very early sign of specific myocardial damage. 329 Figure 1Electrical risk score parameters.

Barriers to Adherence to Iron Chelation Therapy in Thalassemia Patients

Background: Thalassemias are the most common inheritable blood disorders requiring regular blood transfusions and iron chelating therapy. Non-adherence to iron chelation therapy increases complications and is a problem in treating thalassemia. To assess the reasons of non-adherence to iron chelating drug in treating thalassemia. Materials and methods: This descriptive cross-sectional study was carried out in the thalassemia ward of Chattogram Maa Shishu-O-General Hospital, Chattogram from July, 2013 to June, 2014. 70 thalassemia patients aged 2-18 years previously treated with iron chelating drugs were included. Parents were interviewed according to a formulated questionnaire based on discontinuation of iron chelating drugs and its reasons. Data were analyzed by both manually and by SPSS-18. Results: About 48.6% patients needed blood transfusion >10 units/year and 62.9% patients were prescribed with iron chelating drugs. Near about half patients (47.7%) did not continued iron chelating therapy till full prescribed period. Deferiprone (31.8%) and combination of deferipronc & desferrioxamine (31.8%) was the most commonly prescribed drug. Deferiprone is the drug to which most of the patients (70%) were adherent and a good number of patients (65%) discontinued desferrioxamine. Financial problem (100%) was the only reason for discontinuation of oral chelator. In case of parenteral chelator, besides finanacial problem (38.5%), time consuming natures (38.5%), need of hospital admission (23%) are the other causes for non-adherence to iron chelation therapy. Conclusion: Financial problem is the main cause of non-adherence to iron chelation therapy. Iron chelating drugs should be available at low cost. Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 45-49

Ferritin Levels Do Not Reflect the Severity of Iron Overload in Diamond Blackfan Anemia

Introduction: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by hypoplastic anemia, congenital malformations and an increased risk to develop malignancies.Until now, treatment of DBA consists of red blood cell (RBC) transfusions, glucocorticoids (GC) and allogeneic hematopoietic stem cell transplantation in a selection of patients. Whereas RBC transfusions are the main cause of IO, elevated iron parameters have also been reported in non-transfusion-dependent DBA patients. Here we investigated the incidence and severity of IO in a well-described cohort of transfusion-dependent and non-transfusion-dependent DBA patients in order to gain more insight in the regulation of iron metabolism in DBA, and to provide clinical guiding to improve the diagnosis and management of IO in DBA. Methods: In this retrospective, observational study we have included twenty-nine pediatric and adult DBA patients for whom at least one serum ferritin level and/or MRI result was available. Ten patients (34%) were classified as transfusion-dependent (TD) (ten or more transfusions during the twelve months prior to evaluation). Non-transfusion-dependent (NTD) patients (66%) were treated with either GC, incidental transfusions or received no treatment. Transfusion burden (transfusion history) was assessed via medical records. Serum ferritin levels ≥250 ng/mL in males and ≥150 ng/mL in females were considered to be elevated. Results of MRI were expressed as liver iron content (LIC) and as cardiac T2* in milliseconds (ms). LIC ≥3 mg/g indicates significant hepatic IO, and LIC ≥7 mg/g is associated with clinical morbidity. Cardiac T2* ≤20 ms indicates significant cardiac IO. Results: In 15/29 (52%) MRI analysis of IO was performed. Hepatic IO (LIC >3 mg/g) was present in 9/29 (31%) of DBA patients, of which 8/9 (89%) had moderate to severe IO (LIC>7mg/g), despite the fact that all but one were treated with chelation therapy. Overall serum ferritin levels and LIC correlated significantly (r=0.7907, p<0.001), and all TD patients with LIC ≥7 mg/g had serum ferritin levels ³400 ng/mL, however, none of the patients had a serum ferritin >1000 ng/mL (Figure 1A). Interestingly, in the NTD group, hepatic IO was present in 2/7 patients (29%), who both only had mildly elevated serum ferritin levels (263 ng/mL and 277 ng/mL) and were not treated with iron chelation therapy. Based on total transfusion burden since birth, patients were classified in distinct groups: nine patients who received ³10 transfusions during life (9/10) were diagnosed with hepatic IO, whilst none of the patients who received <10 transfusions were diagnosed with hepatic IO. Both mean serum ferritin levels and mean LIC values were significantly higher in patients with ³10 transfusions compared to all with <10 transfusions (Figure 1B-C). Discussion: We demonstrate that IO is common in DBA yet can be easily overlooked in NTD patients that were treated with transfusions in the past. While serum ferritin levels significantly correlated with LIC values, this parameter cannot be used exclusively to screen for IO or titrate iron chelation therapy. We conclude that in clinical practice, biochemical parameters in combination with transfusion history justify a low-threshold to perform an MRI-based evaluation of IO, and to start adequate chelation therapy. Figure 1 Figure 1. Disclosures Van Beers: Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Novartis: Research Funding; RR Mechatronics: Research Funding. Wijk: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Axcella health: Research Funding; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Iron Chelation Therapy in Low- to Intermediate- Risk Myelodysplastic Syndrome Patients: A Systematic Review and Meta-Analysis

Background Transfused patients with low- to intermediate-risk myelodysplastic syndromes (MDS) are known to suffer from iron overload. Iron chelation therapy (ICT) may improve outcomes, however, it remains to be thoroughly investigated. Methods We conducted a systematic review and meta-analysis to assess the benefit of ICT in patients with MDS. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for studies on ICT for low- to intermediate-risk MDS that reported adjusted hazard ratios (aHR) or overall survival (OS). Two reviewers independently screened titles and abstracts and subsequent full texts for eligibility. Studies were extracted for general demographics, AML progression rate, incidence of cardiac injury, and median OS or aHR. aHR risk ratios were calculated using a random-effects model meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and Newcastle-Ottawa scale for non-randomized studies. Results The initial search yielded 1177 citations, of which we included 11 observational studies (n = total patient number) and one RCT (n = total patient number) for analysis. The heterogeneity was moderate (I 2=57%; P=0.02). There was a significant reduction in risk of mortality in patients with iron overload and low- or intermediate-risk MDS treated with ICT (aHR 0.43; 95% CI 0.32-0.57; P < 0.00001) (figure 1). The median OS among patients receiving ICT and patients receiving no ICT was reported for nine studies. The median OS for patients receiving ICT was consistently longer than the median OS in the non-ICT group across all studies (figure 2). Conclusion Iron chelation therapy (ICT) is associated with a lower risk of mortality in low- to intermediate- risk myelodysplastic syndrome patients. Given the limited number of RCTs, more high-quality studies are required before ICT becomes a standard of care for this group of patients Figure 1 Figure 1. Disclosures Crowther: Syneos Health: Honoraria; Precision Biologicals: Honoraria; Pfizer: Speakers Bureau; CSL Behring: Speakers Bureau; Bayer: Speakers Bureau; Hemostasis reference laboratories: Honoraria.

Real-world assessment of myelodysplastic syndrome: Japanese claims data analysis

Aim: To describe the treatment landscape and associated economic burden for myelodysplastic syndrome in Japan. Methods: We studied nationwide retrospective claims data from 2008 to 2019. The study cohort was categorized into patients receiving transfusion, erythropoiesis-stimulating agent, erythropoiesis-stimulating agent + transfusion, azacitidine, azacitidine + transfusion and others. Results: Our study found that the azacitidine + transfusion group had the highest medical cost and severity of disease compared with the other groups. In those patients, healthcare resource utilization and the costs of transfusions, including iron chelation therapy, increased medical costs. Conclusion: Our retrospective analysis provides a current snapshot of real-world treatment patterns and associated incremental economic costs of iron chelation therapy with the presence of transfusions that drive an increase in total costs.