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

Abstract 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.

Download Full-text

Testicular function in patients with regular blood transfusion for thalassemia major

Asian Biomedicine ◽

10.5372/1905-7415.0902.385 ◽

2015 ◽

Vol 9 (2) ◽

Cited By ~ 1

Author(s):

Sukumarn Siripunthana ◽

Taninee Sahakitrungruang ◽

Suttipong Wacharasindhu ◽

Darintr Sosothikul ◽

Vichit Supornsilchai

Keyword(s):

Blood Transfusion ◽

Chelation Therapy ◽

Cell Function ◽

Iron Chelation ◽

Thalassemia Major ◽

Delayed Puberty ◽

Control Group ◽

Blood Transfusions ◽

Testicular Function ◽

Iron Chelation Therapy

AbstractBackgroundRegular blood transfusion and iron chelation therapy have improved the quality of life of patients with thalassemia and increased their longevity, but transfusion also increases the frequency of endocrine complications, possibly because of iron deposition in the pituitary gland or the gonads, or both.ObjectiveTo evaluate testicular function in patients with thalassemia major by basal hormonal study, and identify risk factors for dysfunction.MethodsWe performed a cross-sectional study of 28 patients with thalassemia major aged 11.7 ± 1.8 (8–14.9) years (15 in prepuberty, 13 in puberty with no delayed puberty) who had regular blood transfusions. A normal control group comprised 64 boys who were matched for age and Tanner genital stage.ResultsThe mean level of serum ferritin in the previous year was 1,575 ± 642 ng/mL, and the onset of blood transfusion was at 3.8 ± 2.3 years and iron chelation therapy was 6.6 ± 2.8 years. The trend for anti-Müllerian hormone levels in patients and controls was similar with age, and although higher in the patients, particularly at Tanner stage II, was not significantly different. Testosterone levels were lower in the patients compared with controls; particularly at Tanner stages IV–V (290.88 vs. 537.4 ng/dL,ConclusionPatients who received regular blood transfusions had normal Sertoli cell function. Leydig cell dysfunction may occur, even though the patients had a normal pubertal onset.

Download Full-text

Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major

New England Journal of Medicine ◽

10.1056/nejm199808133390701 ◽

1998 ◽

Vol 339 (7) ◽

pp. 417-423 ◽

Cited By ~ 268

Author(s):

Nancy F. Olivieri ◽

Gary M. Brittenham ◽

Christine E. McLaren ◽

Douglas M. Templeton ◽

Ross G. Cameron ◽

...

Keyword(s):

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelation Therapy

Download Full-text

Computed tomography scanning of the liver to determine efficacy of iron chelation therapy in thalassemia major

The Journal of Pediatrics ◽

10.1016/s0022-3476(89)80564-5 ◽

1989 ◽

Vol 114 (3) ◽

pp. 427-430 ◽

Cited By ~ 5

Author(s):

Nancy F. Olivierl ◽

Dan Grisaru ◽

Allan Daneman ◽

David J. Martin ◽

Vera Rose ◽

...

Keyword(s):

Computed Tomography ◽

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelation Therapy ◽

Computed Tomography Scanning ◽

Tomography Scanning

Download Full-text

Effect of Age at the Start of Iron Chelation Therapy on Gonadal Function in β-Thalassemia Major

New England Journal of Medicine ◽

10.1056/nejm199009133231104 ◽

1990 ◽

Vol 323 (11) ◽

pp. 713-719 ◽

Cited By ~ 99

Author(s):

Naomi Bronspiegel-Weintrob ◽

Nancy F. Olivieri ◽

Beverley Tyler ◽

David F. Andrews ◽

Melvin H. Freedman ◽

...

Keyword(s):

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelation Therapy ◽

Gonadal Function ◽

Effect Of Age

Download Full-text

The Palatability and Tolerability of Deferasirox (Exjade®) Taken with Meals, Different Liquids, or Crushed and Added to Food

Blood ◽

10.1182/blood.v116.21.5155.5155 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5155-5155

Author(s):

Stuart L Goldberg ◽

Patricia Giardina ◽

Joan Parkhurst Cain ◽

Deborah Chirnomas ◽

Jason Esposito ◽

...

Keyword(s):

Adverse Events ◽

Serum Ferritin ◽

Research Funding ◽

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelation Therapy ◽

Age Group ◽

Baseline Serum ◽

Off Label

Abstract Abstract 5155 Introduction: Deferasirox (Exjade®, Novartis Pharmaceuticals) is an oral iron chelator indicated for the treatment of transfusional iron overload. The recommended mode of administration is to be taken on an empty stomach in water, apple juice or orange juice ≥30 minutes before food. However, there have been post-marketing reports of discontinuation or reduced compliance of deferasirox secondary to palatability and gastrointestinal adverse events. Registration trials with deferasirox did not evaluate different food combinations in an attempt to maintain predictable plasma levels. Early single dose studies suggested that the bioavailability of deferasirox is increased when administered with or before meals, and is positively influenced by fat content, but is not affected by degree of dispersion nor type of liquid. Long-term pharmacokinetic and tolerability studies involving a food effect have not been conducted to date, and the ability of alternate methods of administration to improve patient compliance with iron chelation therapy is unknown. Method: This is an ongoing single-arm, open-label, multi-center study designed to evaluate the palatability, safety, tolerability and pharmacokinetics of deferasirox when administered with food, dispersed in any liquid of choice, or crushed and added to food. The patient population includes patients with transfusional hemosiderosis (minimum entry serum ferritin ≥500 μ g/L) aged >2 years with thalassemia major, sickle cell disease (SCD), low or intermediate (INT-1) risk MDS or other anemias, who are on, starting, or resuming treatment with deferasirox. The study began with a 1-month run-in phase with deferasirox dosed according to prescribing information, then a 3-month assessment phase where subjects could choose each week from 5 general administration options including with or without meals, in the morning or evening, crushed and added to a soft food, or mixed in a liquid of choice. Subject diaries are used to record the meal and method of administration at the end of each week. Palatability is assessed with a modified facial hedonic scale, with additional directed questions capturing gastrointestinal side effects. This is a data analysis of the run-in phase. Result: Target enrollment has been met with 65 patients. Baseline data on the first 58 subjects include 8 in the 2 to <10 years of age group (median 7.5 years; range 3–9); 42 in the 10 to <60 years of age group (median 18.5 years; range 10–48); and 8 in the ≥60 years of age group (median 74 years; range71-83). Underlying hematologic diagnoses included SCD (41%), thalassemia major (29%), MDS (12%) and other anemias (17%). Sixty-nine percent of subjects were receiving deferasirox prior to entering the study. The median baseline serum ferritin level was 2405 μ g/L (range 560–8660) and was distributed as shown in Table 1. The most frequent adverse events were diarrhea (19%) and nausea (9%) (Table 2), which were more common in MDS (P=0.23 and P<0.01, respectively). Conclusion: This ongoing trial (NCT00845871) is evaluating whether alternative modes of administration improve palatability and tolerability while maintaining safety. Preliminary data from the assessment phase (deferasirox taken with meals, different liquids, or crushed and added to food) will be presented at the meeting. Disclosures: Goldberg: Novartis Oncology: Consultancy, Honoraria, Research Funding, Speakers Bureau. Off Label Use: Exjade, iron chelation therapy, off-label method of administration. Giardina:Novartis: Research Funding. Parkhurst Cain:Novartis: Research Funding. Chirnomas:Novartis: Research Funding. Esposito:Novartis: Employment. Paley:Novartis: Employment. Vichinsky:Novartis: Consultancy, Research Funding, Speakers Bureau; Hemaquest: Consultancy, Membership on an entity's Board of Directors or advisory committees; Apotex: Consultancy, Research Funding.

Download Full-text

Clinical Effectiveness of Iron Chelation Therapies in Syrian Patients with β Thalassemia Major: Suboptimal Clinical Outcomes and High Prevalence of Iron Overload

Blood ◽

10.1182/blood.v122.21.1719.1719 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1719-1719

Author(s):

Youssef A Lama ◽

Hanan Touma ◽

Khawla AlKeba ◽

Osama Maksoud

Keyword(s):

Combination Therapy ◽

Iron Overload ◽

Chelation Therapy ◽

Iron Chelation ◽

Clinical Effectiveness ◽

Thalassemia Major ◽

Iron Chelation Therapy ◽

Ferritin Concentration ◽

Therapeutic Outcomes ◽

High Prevalence

Abstract Background Thalassemia is the most prevalent autosomal abnormality in the population of Syria. In 2013, the total number of registered thalassemia patients is 8300. Disease prevalence is reinforced by the high rate of consanguineous marriages especially in the rural regions of this Middle Eastern and Mediterraneancountry. Regular blood transfusions and iron chelation therapy (ICT) have significantly improved survival and reduced morbidity of patients withβ thalassemia major (BTM). Although ICTs are provided free of charge by the government to all (BTM) patients, adequate monitoring of therapeutic outcomes is lacking, and cardiac complications still represent significant morbidity and remain the leading cause of mortality. Objective This study aimed at evaluating the prevalence of poor chelation in Syrian patients with BTM, and assessing the effectiveness of different iron chelation regimens provided by the National Thalassemia Program. Methods We conducted a single-centered study encompassing two phases; i) a retrospective chart review of serum ferritin levels of all female and male patients (≥ 3y) with (BTM) receiving iron chelation regimens (mono- or combination therapy) in 2009 and 2010; and ii) a 15 month prospective observational study to evaluate the effectiveness of desferrioxamine (DFO) monotherapy (at a dose of 40-50 mg/kg given over 8–10 h on 5-7 d/week), versus DFO (at the same dose used for DFO monotherapy) in combination with deferiprone (DFP) (at a dose of 75 mg/kg/day) [DFO+DFP] in patients received prior monotherapy with DFO but had poor response. Endpoints were defined as reducing iron stores in iron overloaded patients and improving cardiac function assessed by left ventricular ejection measurements using Doppler Echocardiogram. Statistical analysis of data sets was performed using Prism Graphpad, version 5. Results A total of 493 records of all patients registered at the National Thalassemia Centre in Homs were evaluated. 280 (56.8%) of these patients were diagnosed with BTM, and 245/280 (87.5%) were receiving iron chelation therapy. The average age was 11.35 ± 5.69 year-old (mean ± SD), age range [3-32 year], and male-to-female sex ratiowas 102:103. 39% of the patients were administered DFO, 30% and 10% received oral deferasirox (DFX) and deferiprone (DFP) respectively, whereas 21% received a combination of [DFO + DFP]. The average ferritin concentration of the study population was 3954.89 ± 1431.37 [range from 1362 to 8656] ug/l in 2009, and 4038.22 ± 1572.49 [range from 1173 to 8210] ug/l in 2010. Strikingly, 98% of patients had iron overload; [15% mild, 35% moderate and 48% severe] in 2009, and [12.3% mild, 42.5% moderate and 45.2% severe] in 2010. Patients on DFX had the lowest ferritin concentrations when compared with these of their peers on the DFO and [DFO + DFP] regimens (P=0.0001 and P=0.02 respectively). Patients of DFX also had the lowest percentage of sever iron overload (31%) in comparison with 58%, 51%, and 40% in patients on DOF, [DFO+DFP], and DFP respectively. In the prospective observational phase of our study, several comparative assessments were conducted. The combination of [DFO+DFP] reduced ferritin concentration by 14% from a mean baseline concentration of 4662.4 ±1266.17 to 3697.1 ±1547.9 (μg/l) after the study 15 month follow up period (P=0.0006), whereas DFO alone was ineffective. Cardiac function decreased by a percentage of (-4.74 ± 12.89) from 68.64%±6.97% to 60.98%±7.22% in patients on DFO (p= 0.0001) and from 67.39%±6.49% to 63.91%±8.51% in patients receiving combination therapy (p= 0.031). Mean decrease was greater in DFO regimen (-10.53 ± 11.89) than that seen in patients on combination therapy (-4.74 ± 12.89) (p= 0.035). Conclusions This study reveals aspects of the current status of ICT outcomes in Syria. Our results prove high prevalence of iron overload in patients with BTM despite their receiving ICTs free of charge. Patients are not achieving target serum ferritin thresholds despite chronic treatment with DFO for iron overload. This may suggest its poor clinical effectiveness within the real-world, and necessitates active measures to improve patients’ compliance. The underlying causes of these suboptimal therapeutic outcomes of all ICT regimens should be further investigated, and the cost-effectiveness of ICTs should be reconsidered by decision makers. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

The Zinc and Copper Levels in Thalassemia Major Patients, Receiving Iron Chelation Therapy

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0000000000001102 ◽

2018 ◽

Vol 40 (3) ◽

pp. 178-181 ◽

Cited By ~ 3

Author(s):

Omid R. Zekavat ◽

Ayda Bahmanjahromi ◽

Sezaneh Haghpanah ◽

Sara Ebrahimi ◽

Nader Cohan

Keyword(s):

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Iron Chelation Therapy

Download Full-text

Supportive care and chelation therapy in MDS: are we saving lives or just lowering iron?

Hematology ◽

10.1182/asheducation-2009.1.664 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 664-672 ◽

Cited By ~ 16

Author(s):

Heather A. Leitch ◽

Linda M. Vickars

Keyword(s):

Iron Overload ◽

Supportive Care ◽

Chelation Therapy ◽

Iron Chelation ◽

Thalassemia Major ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Beta Thalassemia ◽

Ventricular Ejection Fraction ◽

The Impact

AbstractThe myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of transformation to acute myeloid leukemia (AML). Although new treatments are available, a mainstay in MDS remains supportive care, which aims to minimize the impact of cytopenias and transfusion of blood products. Red blood cell (RBC) transfusions place patients at risk of iron overload (IOL). In beta-thalassemia major (BTM), IOL from chronic RBC transfusions inevitably leads to organ dysfunction and death. With iron chelation therapy (ICT), survival in BTM improved from the second decade to near normal and correlated with ICT compliance. Effects of ICT in BTM include reversal of cardiac arrhythmias, improvement in left ventricular ejection fraction, arrest of hepatic fibrosis, and reduction of glucose intolerance.It is not clear whether these specific outcomes are applicable to MDS. Although retrospective, recent studies in MDS suggest an adverse effect of transfusion dependence and IOL on survival and AML transformation, and that lowering iron minimizes this impact. These data raise important points that warrant further study. ICT is potentially toxic and cumbersome, is costly, and in MDS patients should be initiated only after weighing potential risks against benefits until further data are available to better justify its use. Since most MDS patients eventually require RBC transfusions, the public health implications both of transfusion dependence and ICT in MDS are considerable. This paper summarizes the impact of cytopenias in MDS and treatment approaches to minimize their impact, with a focus on RBC transfusions and their complications, particularly with respect to iron overload.

Download Full-text