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Cappellini M.D.,University of Milan | Bejaoui M.,Center National Of Greffe Of Moelle Osseuse | Agaoglu L.,Istanbul University | Canatan D.,Suleyman Demirel University of Turkey | And 14 more authors.
Blood | Year: 2011

Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years'exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β- thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. © 2011 by The American Society of Hematology.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-1 | Award Amount: 7.63M | Year: 2011

-thalassaemia major is one of the most severe forms of chronic congenital anaemia. The recommended treatment consists in regular blood transfusions combined with chelating therapy to remove harmful iron accumulation in the body. The use of deferoxamine, the first chelating agent only available for subcutaneous administration is limited due to toxicity and the lack of compliance, despite its satisfactory therapeutic effects. An oral iron chelating agent, deferiprone, was authorised in Europe in August 1999 and recommended for the treatment of iron overload in patients with thalassaemia major when deferoxamine is contraindicated or inadequate. Despite a wide experience of the administration of deferiprone for thalassaemic patients, limited data are available on its use in children below 10 years and the need for additional data in this age subset was clearly indicated in the 2009 priority list approved by the Paediatric Committee at the European Medicines Agency (PDCO). In addition, according to the recent scientific advancements and in consideration of the anticipated benefit of this chelator in controlling cardiac iron overload, studies evaluating the effects of the deferiprone in all the paediatric ages and in all transfusion-dependent chronic congenital anaemia (including Sickle Cell Diseases) were also considered a critical therapeutic need. The DEEP project, in line with these premises, has been funded with the specific aim to produce a new oral liquid formulation of deferiprone suitable for the paediatric use and to provide evidences for the use of this chelator as first line therapy in the whole paediatric population (from 1 month to 18 years) affected by transfusion-dependent chronic anaemia. The condition under study in the DEEP project is rare. This poses special difficulties in the conduct of the studies due to the small patient population and the need to involve a large number of recruiting centres . However, being dedicated to develop an orphan drug, DEEP has been also recognised in the context of IRDiRC, the International Rare Diseases Research Consortium devoted to repurpose/develop 200 new drugs for Rare Diseases by the end of 2020. Main features of the DEEP project are: -The innovative design of the clinical studies including pharmacokinetic modelling for the definition of the most appropriate dosage of deferiprone in younger children, the cardiac MRI T2* evaluation as primary endpoint, a three years safety study aimed at evaluating deferiprone, in monotherapy or in combination, in the real worlds setting and, for the first time, a comparative efficacy-safety trial to compare the two existing oral chelators: deferiprone and deferasirox. -The DEEP Consortium including European and non-European Countries from the Mediterranean region where the transfusion-dependent congenital anaemia, in particular -thalassemia major, is particularly widespread: the collaboration within a multinational and multicultural network makes the Project extremely challenging due to many different ethical, methodological and social approaches to be explored and positively addressed.

Imen M.,University of Tunis | Ikbel B.M.M.,University of Tunis | Leila C.,University of Tunis | Fethi M.,Center National Of Greffe Of Moelle Osseuse | And 3 more authors.
American Journal of Human Biology | Year: 2011

Objectives: The polymorphism of the β-globin gene haplotypes and frameworks is useful in the determination of the unicentric and multicentric origin of a mutational event. In our study, the haplotypes linked to the Tunisian β S mutation are determined to improve our knowledge of the chromosomal background of the β-globin gene in sickle-cell anemia in Tunisia. Methods: The authors have investigated 242 unrelated individuals. Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism-based methods. Seven polymorphic sites in the β-globin gene cluster were examined. The correlation of these various haplotypes with Hb F expression was studied. Results: The Benin haplotype (Ben) was largely predominant (60.54%) followed by the Atypical haplotype A (8.43%) and Bantu (Ban) (2.71%) haplotypes. A total of 94 chromosomes had atypical haplotypes, 78 (23.49%) had A1 [-----++], 11 (3.31%) had A2 [-------], and five (1.5%) had B1 [--+--++]. The Benin haplotype is associated with a fairly low HbF levels. Conclusion: The very high frequency of the Benin haplotype in our study suggests that the β S mutation present in Tunisia may have originated from the Benin region and was brought to Tunisia along the slave trade routes. However, another atypical haplotype observed a new emergence in our population and could be considered as specific to Tunisian chromosome β S. © 2011 Wiley-Liss, Inc.

Bejaoui M.,Center National Of Greffe Of Moelle Osseuse | Guirat N.,Center National Of Greffe Of Moelle Osseuse
Mediterranean Journal of Hematology and Infectious Diseases | Year: 2013

Beta-thalassemia major (TM) remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months-31 years) were included in the study. The majority originated from the north west of the country.A moderate iron overload between 1501 and 2500 ng/ml was found in 61patients, while 81 patients (26.9%) had a ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%). 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social s and health benefits.

Mechergui A.,Center National Of Greffe Of Moelle Osseuse | Achour W.,Center National Of Greffe Of Moelle Osseuse | Ben Hassen A.,Center National Of Greffe Of Moelle Osseuse
World Journal of Microbiology and Biotechnology | Year: 2014

We aimed to compare accuracy of genus and species level identification of Neisseria spp. using biochemical testing and 16S rRNA sequence analysis. These methods were evaluated using 85 Neisseria spp. clinical isolates initially identified to the genus level by conventional biochemical tests and API NH system (Bio-Mérieux®). In 34 % (29/85), more than one possibility was given by 16S rRNA sequence analysis. In 6 % (5/85), one of the possibilities offered by 16S rRNA gene sequencing, agreed with the result given by biochemical testing. In 4 % (3/85), the same species was given by both methods. 16S rRNA gene sequencing results did not correlate well with biochemical tests. © 2014 Springer Science+Business Media Dordrecht.

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