A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in ß-thalassemia major (CORDELIA).

Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 ß-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938.

Misdiagnosis of Hb D-Punjab/ß-thalassemia is a potential pitfall in hemoglobinopathy screening programs: a case report.

Compound heterozygosity for Hb D-Punjab [ß121(GH4)Glu→Gln, GAA>CAA] /ß-thalassemia (ß-thal) must be carefully differentiated from homozygous Hb D-Punjab in premarital screening. This is essential when the partner is a carrier of ß-thal trait. The case of a baby born affected with ß-thal major (ß-TM), from a marriage between a mother with ß-thal trait and a father with Hb D-Punjab/ß-thal, is presented. The father had been misdiagnozed as homozygous Hb D-Punjab during premarital screening, even though the screening program utilized complete blood counts and high performance liquid chromatography (HPLC). The factors that may have contributed to this midsiagnosis are presented and discussed. It is recommended that cases of Hb D-Punjab, or any other hemoglobin (Hb) variant appearing as homozygous, are carefully evaluated if microcytic hypochromic parameters not associated with α-thal are present. In all cases of suspected hemizygosis, molecular analysis should always be performed, and in particular if one partner is a ß-thal carrier.

Hemoglobinopathy carrier prevalence in the United Arab Emirates: first analysis of the Dubai Health Authority premarital screening program results.

The aim of this study was to determine the prevalence of hemoglobinopathy carriers in United Arab Emirates (UAE) nationals subjected to mandatory premarital screening in Dubai over a 4-year period. Data from UAE nationals who underwent premarital screening by the Dubai Health Authority between January 2007 and December 2010 were collected and analyzed. Premarital screening in Dubai is based on complete blood counts (CBC) and hemoglobin (Hb) high performance liquid chromatography (HPLC). Among the 6,420 UAE nationals screened, 8.5% (n = 545) were suspected to be carriers. The following carrier frequencies were observed: ß-thalassemia (ß-thal), 4.56% (n = 293); Hb S [ß6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T], 2.9% (n = 186); Hb D-Punjab [ß121(GH4)Glu→Gln, GAA>CAA; HBB: c.364G>C], 0.78% (n = 50); Hb Lepore (뫧 hybrid gene) with an undetermined molecular genotype, 0.17% (n = 11); Hb E [ß26(B8)Glu→Lys, GAG>AAG; HBB: c.79G>A], 0.03% (n = 2); and hereditary persistence of fetal Hb (HPFH), 0.016% (n = 1). Hb E-Hb S and Hb E-ß-thal also occurred at a rate of 0.016% (n = 1) each; and 0.87% (n = 56) subjects were suspected of carrying silent ß-thal. The prevalence of ß-thal trait was consistent with the prevalence published by others in the region. Silent ß-thal is challenging for screening programs, and is expected to arise in populations with a high prevalence of ß-thal carriers. The prevalence of Hb S trait observed in this study was lower than that in other reports for the region. New cases of ß-thal major (ß-TM) still arise because many fertile couples got married before the screening programs were implemented, and pregnancy termination is not widely practiced in the UAE due to religious restraints. Moreover, some couples choose not to have prenatal diagnosis (PND) or pre implantation genetic diagnosis (PGD), even if they are aware of their risk status. The prevalence of ß-thal trait in the UAE is high. This justifies efforts to control the disease by holding regular community awareness and screening programs, performing premarital screening and genetic counseling, and making PND and PGD available to couples who request it.

Serum ferritin levels and endocrinopathy in medically treated patients with ß thalassemia major.

The association between iron overload indices and pathology of the heart and liver in transfusion-dependent patients with ß thalassemia major (TM) has been extensively studied. Nonetheless, data on endocrine disease remains limited. This was a cross-sectional study of 382 TM patients treated with regular transfusions and desferrioxamine at the Thalassemia Center in Dubai, UAE. Retrieved data included demographics, splenectomy status, steady-state serum ferritin levels, and the presence of endocrinopathies (diabetes mellitus, hypothyroidism, hypoparathyroidism, and hypogonadism). Multivariate logistic regression analyses were used to determine which variables were independently associated with the occurrence of each endocrinopathy. The mean age of patients was 15.4 ± 7.6 years, with an equal sex distribution. The mean serum ferritin level was 2597.2 ± 1976.8 µg/l. The frequencies of specific endocrinopathies were diabetes mellitus (10.5%), hypothyroidism (6.3%), hypoparathyroidism (10.5%), and hypogonadism (25.9%). On multivariate logistic regression analysis, patients with a serum ferritin level >2,500 µg/l, but not >1,000-2,500 µg/l, were 3.53 times (95% CI 1.09-11.40) more likely to have diabetes mellitus, 3.25 times (95% CI 1.07-10.90) more likely to have hypothyroidism, 3.27 times (95% CI 1.27-8.39) more likely to have hypoparathyroidism, and 2.75 times (95% CI 1.38-5.49) more likely to have hypogonadism compared to patients with a serum ferritin level ≤1,000 µg/l. However, splenectomized patients with serum ferritin levels ≤2,500 µg/l had comparably high rates of all endocrinopathies as patients with serum ferritin levels >2,500 µg/l. Endocrinopathy is common in TM patients treated with desferrioxamine therapy, especially in patients with serum ferritin levels >2,500 µg/l or those splenectomized.