Survival in Medically Treated Patients with Homozygous β-Thalassemia

Olivieri, Nancy F.; Nathan, David G.; MacMillan, James H.; Wayne, Alan S.; Liu, Peter P.; McGee, Allison; Martin, Marie; Koren, Gideon; Cohen, Alan R.

doi:10.1056/nejm199409013310903

Cited by 812 publications

(598 citation statements)

References 23 publications

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“…Median serum ferritin levels in both patient groups at month 24 were lower than the threshold of 2500 ng/mL, which is associated with increased morbidity and mortality [22,23]. In parallel, mean LIC was reduced to below the threshold of 15 mg Fe/g dw by month 24, indicating a substantial reduction in iron burden (from baseline values above 30 mg Fe/g dw; considerably higher than in other monotherapy and combination therapy studies [9,10]) and a reduced risk of progressive organ damage and early death [24,25].…”

Section: Discussionmentioning

confidence: 83%

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

et al. 2014

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Long‐term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion‐dependent beta thalassemia patients. In a 1‐year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ≥ 10 ms) or liver (LIC <15 vs. ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long‐term safety profile of deferasirox or DFO was consistent with previous reports; serious drug‐related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron‐overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron (Clinicaltrials.gov identifier: NCT00600938). Am. J. Hematol. 90:91–96, 2015. © 2014 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 83%

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

et al. 2014

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“…The greater the body iron burden, the greater the risk of cardiac disease. One study in thalassaemia major patients found that those with at least two-thirds of serial serum ferritin estimations less than 2,500 mg/L had significantly less cardiac disease than those with higher levels [10]. Brittenham et al [11] studied 59 thalassaemia major patients who were more than 7 years old.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of QT dispersion in β thalassaemia major patients

et al. 2006

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Cardiac complications are considered to be the primary cause of death in patients with b thalassaemia major. QT dispersion is a marker variability of ventricular repolarization and is elevated in various high risk groups of patients. This study was carried out in patients with b thalassaemia major to evaluate QT dispersion and to investigate the relationship between QT dispersion and body iron load. Sixty-two b thalassaemia major patients were enrolled into the study. The average serum ferritin levels and liver iron concentration was assessed. For each patient, QTQTc intervals and QT-QTc dispersions were calculated and V1S and V5R were measured. All the subjects underwent two-dimensional M mode echocardiogram and Doppler study. LVMI was found higher in thalassaemia major patients compared to control group. b thalassaemia major patients showed significantly higher mean QT, QTc, QTd, and QTcd values compared to the control group. The mean V5R and V1S amplitudes were also higher in b thalassaemia major patients. There was a positive correlation between LVMI and QTc, QTd and QTcd. However, there was no significant correlation between QT dispersion and serum ferritin and liver iron concentration. Prospective longitudinal studies are needed to assess the prognostic significance of these findings. Am. J. Hematol. 81:901-906, 2006. V V C 2006 Wiley-Liss, Inc.

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“…Ferritin is the most frequently used measure as it is inexpensive, widely available, and reliable, with extensive clinical validation in monitoring iron status. Ferritin measurements have prognostic value, as demonstrated by recent studies, one of which identified cardiac-related mortality greater than 80% over 15 years among patients with thalassemia in whom more than 67% of ferritin measurements exceeded 2,500 ng/mL [6,7]. However, in individuals the predictive value of ferritin is limited by inflammation and vitamin C deficiency.…”

Section: Serum Markers Of Iron Statusmentioning

confidence: 97%

Diagnosis and management of transfusion iron overload: The role of imaging

Wood

2007

Am. J. Hematol.

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The characterization of iron stores is important to prevent and treat iron overload. Serum markers such as ferritin, serum iron, iron binding capacity, transferrin saturation, and nontransferrin‐bound iron can be used to follow trends in iron status; however, variability in these markers limits predictive power for any given individual. Liver iron represents the best single marker of total iron balance. Measures of liver iron include biopsy, superconducting quantum interference device, computer tomography, and magnetic resonance imaging (MRI). MRI is the most accurate and widely available noninvasive tool to assess liver iron. The main advantages of MRI include a low‐rate of variability between measurements and the ability to assess iron loading in endocrine tissues, the heart and the liver. This manuscript describes the principles, validation, and clinical utility of MRI for tissue iron estimation. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

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Survival in Medically Treated Patients with Homozygous β-Thalassemia

Abstract: The prognosis for survival without cardiac disease is excellent for patients with thalassemia major who receive regular transfusions and whose serum ferritin concentrations remain below 2500 ng per milliliter with chelation therapy.

Cited by 812 publications

References 23 publications

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine

Evaluation of QT dispersion in β thalassaemia major patients

Diagnosis and management of transfusion iron overload: The role of imaging

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