The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

Deferasirox administration for the treatment of non-transfusional iron overload in patients with thalassaemia intermedia

Abnormal iron regulation in patients with thalassaemia intermedia may lead to iron overload even in the absence of transfusions. There are limited data on iron chelator use in patients with thalassaemia intermedia and no guidelines exist for the management of iron overload. We present data from 11 patients with thalassaemia intermedia treated with deferasirox (Exjade®, 10-20 mg/kg/d) for 24 months. Liver iron concentration and serum ferritin levels significantly decreased over the first 12 months (P = 0·005) and continued to decrease over the remainder of the study (P = 0·005). This small-scale study indicated that deferasirox may be suitable for controlling iron levels in patients with thalassaemia intermedia. © 2010 Blackwell Publishing Ltd

Cardiac magnetic resonance in transfusion dependent thalassaemia: Assessment of iron load and relationship to left ventricular ejection fraction

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0.57, P &lt; 0.001). The prevalence of CD was 32.9% in patients with T2* ≤ 8 ms, 12.5% in patients with T2* &gt; 8 ms and ≤14 ms and reduced to 9.1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0.68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible. © 2010 Blackwell Publishing Ltd

Thirty-year experience in preventing haemoglobinopathies in Greece: Achievements and potentials for optimisation

Objectives: Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. Methods: Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. Results: Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P &lt; 0.001). Unawareness and parental choice were more frequent in SCD compared to β-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β-TM and SCD, respectively. Conclusions: The β-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling. © 2013 John Wiley &amp; Sons A/S

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: A clinical observational study

Background. Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR. Results. For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis (&quot;Initial interval analysis&quot;) assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline. Conclusion. With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR. © 2009 Berdoukas et al; licensee BioMed Central Ltd

HBeAg-negative hepatitis B in a previously thalassemic patient during immunosuppressive therapy for chronic GVHD

We report the case of a 15-year-old previously thalassemic girl who, 15 months after allogeneic BMT, developed HBeAg-negative hepatitis B (variant with mu-1896). In the absence of another route of transmission, HBV reactivation is postulated. The time of emergence of the HBV variant (with mu-1896) is probably related to the development of anti-HBe immunity. This mutant strain is associated with fulminant hepatitis. The patient achieved complete remission and HBV eradication despite having moderate GVHD and receiving immunosuppressive therapy

The different patterns of insulin response during oral glucose tolerance test (Ogtt) in transfused young patients with β-thalassemia

Background and aim: Dysregulation of glucose metabolism is a common complication of transfusions in Transfusion Dependent Thalassemia (TDT) patients. For early diagnosis of glucose disturbances, screening is recommended. The age of starting and the type of screening vary; the more common methods are assessment of RPG, FPG, 2h PG and 2 hours OGTT. The combined assessment of glucose tolerance and insulin response during OGTT is rarely recommended. The main objective of the study is the evaluation of simultaneous assessment of Glucose Tolerance (GT) and Insulin Response (IR) during OGTT in patients with TDT. Methods: 43 TDT patients aged 12-28years, without clinical evidence of glucose disturbances, were randomly selected for the study. The 2-hour OGTT in 30 minutes intervals was applied. Plasma glucose and insulin were assessed in all samples using routine laboratory methods. Results: Of 43 patients 31(72%) had Normal GT; of them 9 (29%) had normal insulin response (NIR), 14 (45%) high IR and 8(26%) delayed peak IR. Delayed peak IR was found in 8 of the 9 patients with Impaired GT and in 2 of the 3 with diabetic GT. Deficient IR (hypoinsulinemia) was found in two patients. Conclusions: Simultaneous assessment of GT and IR during OGTT in TDT patients, seems to be a most sensitive and creditable screening test for early diagnosis of glucose disturbances. High IR and delayed peak IR in normoglycemic patients are valuable indices for diagnosis of the pre-diabetic state that precede the development of glucose disturbances in TDT patients and start proper follow and management. (www.actabiomedica.it). © Mattioli 1885

Variations of ferritin levels over a period of 15 years as a compliance chelation index in thalassemic patients

We studied the changing pattern of the distribution of ferritin levels in 430 regularly-transfused patients with thalassemia in an attempt to evaluate compliance of chelation with deferoxamine. The study covered 15 years and was divided in three periods: 1981-1985, 1986-1990, and 1991-1995. The patients were stratified in age-groups. The mean ferritin levels of each period were calculated for each patient individually. The study showed that: (i) When all the patients were compared as a group, there was a significant decrease in mean ferritin between 1981-1985 and 1991-1995, despite a significant change in the patients’ mean age; (ii) When patients of same age were compared between periods, there was a decrease in mean ferritin between 1981-1985 and 1991-1995, as well as a decrease in the proportion of patients with ferritin &gt; 4000 mug/L, with a parallel increase in the proportion of patients who had ferritin &lt; 2000 mug/L; (ill) When the same patients were followed longitudinally, they showed a decrease in their ferritin levels in all age groups with the exception of the late adolescence period. The decrease in iron overload observed in patients on close follow up implies that compliance with chelation therapy has improved with time and therefore, a favourable influence in survival could be expected. (C) 2001 Wiley-Liss, Inc