Successful chelation in beta-thalassemia major in the 21st century.

This century has seen a revolution the management of beta-thalassemia major. Over a 12-year period to 2016, we aimed to analyze the benefits of such advances. In 209 patients, independent of the chelation regimen, ferritin, cardiac T2* and liver iron concentration changes were evaluated. We defined chelation success (ChS) as no iron load in the heart and acceptable levels in the liver. Over 3 early magnetic resonance imagings, the same parameters were assessed in 2 subgroups, the only 2 that had sufficient patients continuing on 1 regimen and for a significant period of time, 1 on deferrioxamine (low iron load patients n = 41, Group A) and 1 on deferoxamine-deferiprone (iron overloaded n = 60, Group B). Finally, 28 deaths and causes were compared to those of an earlier period. The 209 patients significantly optimized those indices, while the number of patients with chelation success, increased from 6% to 51% (P < .0001). In group A, ChS after about 8 years increased from 21 to 46% (P = .006), while in Group B, from 0% to 60% (P < .001) after about 7 years. Deaths over the 2 periods showed significant reduction. Combined clearance of cardiac and liver iron (ChS) is feasible and should become the new target for all patients. This requires, serial magnetic resonance imagings and often prolonged intensified chelation for patients.

Chronic Hemolysis May Adversely Affect Skeletal Health. A Cross-Sectional Study of a Pediatric Population.

Hereditary hemolytic disorders cause ineffective erythropoiesis and bone marrow hyperplasia. Little is known about their effect on growth and skeletal health. The aim of this study was to evaluate growth, bone and body composition of non transfusion-dependent (NTD) pediatric patients with chronic hemolysis. A detailed history and clinical examination, dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS) and total body less head (TBLH) and bone turnover markers were performed. Thirty-nine patients (22 males and 17 females, 20 prepubertal), aged 11.4 ± 3.6 years [14 had ß-thalassemia intermedia (ß-TI), 17 α-thalassemia (α-thal) and eight hereditary spherocytosis (HS)] were evaluated. Fifty-seven previously studied controls were used for statistical analysis. The patients had lower weight and body mass index (BMI) (Z-scores -0.2 and -0.3, respectively, p < 0.05). Post-traumatic fractures were reported by 28.0% of the patients. Compared to controls, they had lower lumbar and subcranial bone mineral density (BMD), as well as reduced fat mass (FM), whereas muscle mass was not affected. One in three patients had low vitamin D and there was increased bone resorption and reduced bone formation. Correlations between different parameters revealed a potential role of osteocalcin, hemoglobin (Hb) and lactate dehydrogenase (LDH) as prognostic markers for bone health, in the setting of chronic hemolysis. Hereditary spherocytosis (HS) patients were the least affected in terms of growth and bone profile. Chronic hemolysis may lead to impaired growth and bone health, even in young, NTD patients. The degree of hemolysis determines bone health risk. Regular surveillance of bone health is justifiable.

Cardiac magnetic resonance imaging R2* assessments and analysis of historical parameters in patients with transfusion-dependent thalassemia.

Recent advances in magnetic resonance imaging (MRI) techniques allow the assessment of iron overload in tissues 1 especially the heart, 2 in transfusion-dependent thalassemia patients. The R2* value (1/T2*) recorded in the intraventricular septum of the heart indirectly measures the degree of cardiac iron load. Applying this new technology we looked at a number of historical and biochemical parameters in order to determine their relationship to cardiac iron overload and the effect of cardiac iron on functional and structural changes of the heart in transfusion-dependent thalassemics.

Predictive echo-Doppler indices of left ventricular impairment in B-thalassemic patients.

Early detection of cardiac-function impairment by echo-Doppler indices can assist in preventing further cardiac damage by modifying disease progression and treatment. We analyzed our thalassemia major patients database with 10 years cardiac follow-up. Included patients were under constant therapy and should have an initial echo-Doppler study with normal Shortening Fraction (SF > 30%) and reexamination within the last year. We identified patients who developed impaired left ventricular (LV) function in the last Echo and we attempted to find which measured indices could predict LV function impairment. Three hundred fifteen of the 632 database patients were enrolled. Twelve of them developed LV systolic dysfunction. There were no statistically significant differences in mean age, ferritin, and pretransfusion hemoglobin levels of the two groups. LV-systolic-dysfunction group was presenting statistically significantly higher LF end-systolic diameter (LVESD) index, lower SF, higher early transmitral peak flow velocities/late transmitral peak flow velocities (A) ratios, lower A value. All other echocardiographic parameters did not differ significantly. By receiver-operating characteristic analysis, we determined systolic and diastolic indices specificity and sensitivity for LV impairment: LVESD 97% specificity, 11% sensitivity (cutoff value 2.44 cm/m(2) ), SF 92.1 and 33.3% (cutoff value 33%). Regarding diastolic indices, A index was the best criterion (97.7% specificity, 25% sensitivity, cutoff value

Correlation of echocardiography parameters with cardiac magnetic resonance imaging in transfusion-dependent thalassaemia major.

BACKGROUND AND OBJECTIVE: Heart iron load (cardiac Fe) can be indirectly quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited, whereas echocardiography (Echo) is relatively inexpensive and readily available. The objective was to find Echo parameters that may be useful for predicting cardiac Fe. DESIGN AND METHODS: We compared a number of parameters derived from Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR study. RESULTS: All patients with decreased left ventricular (LV) function had cardiac Fe. After removing those patients from the analysis, the total diameter index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9% respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2 or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%, respectively, but with low sensitivity. INTERPRETATION AND CONCLUSIONS: Echo parameters for cardiac Fe prediction have restricted value, whereas CMR is essential to assess cardiac Fe. However, patients with decreased LV systolic function should be considered a priori as having cardiac Fe, and chelation therapy should be intensified. This also applies to patients who have the above-described Echo criterion values, even if CMR is not available. Once a patient is found by CMR to have cardiac Fe, then the above Echo criterion values may be useful for ongoing monitoring.