Showing papers by "Maria Domenica Cappellini published in 2008"
TL;DR: The Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders, and the resulting recommendations advise about which examination to carry out in order to planIron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelated therapy, and when and how to switch standard therapy.
Abstract: New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.
189 citations
TL;DR: The molecular and cellular mechanisms leading to hypercoagulability in beta-thalassemia are reviewed, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types ofThalassemias.
144 citations
TL;DR: This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration.
Abstract: Enzyme replacement was introduced as treatment for non-neuronopathic Gaucher disease more than 15 years ago. To ensure the best use of this costly ultra-orphan agent, a systematic disease management approach has been proposed by an international panel; this includes the development, by consensus, of achievable treatment goals. Here we critically review these goals and monitoring guidelines and incorporate emerging experience of the disease in the therapeutic era, as well as contemporary clinical research. This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration. In addition, we identify key areas for development, including the requirement for a validated index of disease severity; the need to correlate widely used biomarkers with long-term disease outcomes, and the desirability of establishing agreed standards for monitoring of bone disease particularly in infants and children with Gaucher disease.
120 citations
TL;DR: Thalassemia intermedia is a highly diverse group of thalassemic syndromes associated with anemia and a range of specific complications, such as extramedullary hematopoiesis, leg ulcers, gallstones and a hypercoagulable state, which are uncommon in patients with thalasemia major.
Abstract: Thalassemia intermedia is a highly diverse group of thalassemia syndromes associated with anemia and a range of specific complications, such as extramedullary hematopoiesis, leg ulcers, gallstones and a hypercoagulable state, which are uncommon in patients with thalassemia major.[1][1] The degree of
104 citations
TL;DR: The study showed that most of the patients with TM had severe psychosocial problems and it was concluded that medical therapy of these patients should be supported with psychological aid and psychiatric treatment.
Abstract: Beta-thalassemia major (TM), a chronic, genetically determined hematological disorder, has received little investigation on the psychological aspects of the disease and the psychosocial adjustment of patients with this anemia. Unfortunately, the few psychological studies referred on the literature are generally limited to the investigation of the only children with thalassemia major. The study was planned to assess the self-image, the quality of life, the way of coping and to investigate the existence of psychiatric disorders in young adults with thalassemia major. 147 patients were included in the study. Patients were psychologically investigated by three interviews: the first connects some psychosocial information, the second submits patients to the psychological test and the third gives back the results obtained by the test. The psychological test consists of the ways of coping questionnaire (WCQ), the Machover’s test, The short form 36-health survey questionnaire (SF-36) and symptom-check-list-90 revised (SCL-90-R) were performed on all patients. Vis-a-vis identity and self-image were found to be low with feeling of insufficiency and being exposed to vulnerability in 80% of patients with TM. Evaluation of mean values of symptomatological dimensions in these patients showed a personality characterized by somatization (SOM), depression (DEP) and obsessive-compulsive traits. The principal coping strategy used is escape-avoidance. No statistically significant differences occurred to relation to gender, age, level education and SCL-90-R and WCQ scores. Estimation of the SF-36 scores showed that the emotional role and social function values were considerably lower than in all of the domain. As a result, the study showed that most of the patients with TM had severe psychosocial problems. Relying on these data, it was concluded that medical therapy of these patients should be supported with psychological aid and psychiatric treatment.
89 citations
TL;DR: The management of β-TM patients undergoing transfusions and ICT is efficacious, although costly, but overall benefits were not always perceived as optimal by patients, so efforts must be focused to improve patients' acceptance and satisfaction with their therapy.
Abstract: Objectives: Iron chelation treatment (ICT) in β-thalassemia major (β-TM) patients undergoing blood transfusions can cause low satisfaction, low compliance, with possible negative consequences on treatment success, patients' wellbeing, and costs. The purpose was to estimate the societal burden attributable to β-TM in terms of direct and indirect costs, health-related quality-of-life (HRQoL), satisfaction and compliance with ICT in patients undergoing transfusions and ICT.Research design and methods: The naturalistic, multicenter, longitudinal Italian-THAlassemia-Cost-&-Outcomes-Assessment (ITHACA) cost-of-illness study was conducted involving patients of any age, on ICT for at least 3 years, who were enrolled at 8 Italian Thalassemia Care Centers. Costs were estimated from the societal perspective, quantified with tariffs, prices, or net earnings valid in 2006.Results: One-hundred and thirty-seven patients were enrolled (median age = 28.3, 3–48 years, 49.6% male) and retrospectively observed for a ...
81 citations
TL;DR: Two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (C-->T), both presenting with a thalassemia intermedia phenotype are described and two new rearrangements are revealed, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element.
Abstract: We describe two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (C-->T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or red cell enzyme deficiencies were excluded. In one case a triplication of the alpha-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the alpha-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-alpha(3.7) triplication in trans, resulting in a total of 7 active alpha-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active alpha-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of alpha-globin genes duplication defects in cases of beta-thalassemia heterozygotes with thalassemia intermedia phenotypes.
80 citations
TL;DR: It is recommended that patients treated with deferasirox are monitored regularly for iron status and adverse events, to ensure that an effective and tolerable iron chelation regimen is established for each individual patient.
73 citations
TL;DR: β-thalassemia intermedia patients can present with a severe clinical disease at 2–6 years of age or remain asymptomatic until adult life, and are usually transfusion independent.
Abstract: CAMASCHELLA C, 1995, HAEMATOLOGICA, V80, P58; Cappellini MD, 2000, BRIT J HAEMATOL, V111, P467, DOI 10.1046-j.1365-2141.2000.02376.x; DIVON MY, 1992, CLIN OBSTET GYNECOL, V35, P156, DOI 10.1097-00003081-199203000-00021; Levy A, 2005, EUR J OBSTET GYN R B, V122, P182, DOI 10.1016-j.ejogrb.2005.02.015; Martins Junior L. M., 2007, Archivos de Zootecnia, V56, P103; Moratelli S, 1998, J PEDIATR ENDOCR MET, V11, P915; Nassar AH, 2006, AM J HEMATOL, V81, P499, DOI 10.1002-ajh.20654; Nassar AH, 2006, J THROMB HAEMOST, V4, P1413, DOI 10.1111-j.1538-7836.2006.01912.x; Pakbaz Z, 2007, PEDIATR BLOOD CANCER, V49, P329, DOI 10.1002-pbc.21275; Skordis N, 1998, J PEDIATR ENDOCR MET, V11, P935; Taher A, 2006, THROMB HAEMOSTASIS, V96, P488, DOI 10.1160-TH06-05-0267; Taher A, 2006, BLOOD CELL MOL DIS, V37, P12, DOI 10.1016-j.bcmd.2006.04.005
57 citations
TL;DR: The GauSSI-I is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment.
Abstract: Background Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment.Design and Methods The new scoring system proposed here, the “Gaucher Disease Severity Score Index – Type I” (GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods on an equivalent basis.Results The new scoring system, GauSSI-I, was developed. Six specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available.Conclusions The GauSSI-I is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment.
57 citations
TL;DR: The results suggest that in 14 days different steps of human erythropoiesis from peripheral CD34(+) cells could be reproduced, with high recovery of highly purified erythroid cells.
Abstract: In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation from BFU-E to mature erythrocytes both in normal and pathological conditions. Most of the available in vitro liquid cultures are from cell lines or are limited by the production of few erythroid cells mixed with myeloid cells. Here we describe an erythroid liquid culture system starting from CD34(+)-enriched cells obtained from peripheral blood. CD34(+) cells were cultured for 21 days in different conditions. Precisely stem cell factor (SCF, 20 ng/mL) and IL-3 (10 ng/mL) were added at starting point plus Epo (3 U/mL) at day 0 or 7 of culture with or without cyclosporine A (Cy; 1 mg/mL). In all the conditions, the highest recovery was obtained at day 14 of culture. Epo and Cy added at day 0 produced the highest cell expansion (170-fold mean amplification of the initial cell input by day 14) and recovery of erythroid cell. Sixty seven percent of the cells were GP(+) at day 7 and 97% by day 14 respectively. Most of the cells were proerythroblasts at day 7 and mature erythroblasts at day 14 (>90% were benzidine(pos)). The presence of Cy favoured erythroid differentiation and maturation and reduced the percentage of non-erythroid CD45(+) cells (2% with Cy versus 5% without Cy). Cells cultured with Epo and Cy reproduced erythropoiesis also at the molecular level. The results suggest that in 14 days different steps of human erythropoiesis from peripheral CD34(+) cells could be reproduced, with high recovery of highly purified erythroid cells. The high number and purity of erythroid cells produced from a small amount of peripheral blood make this method useful for studying either normal or pathological erythropoiesis.
TL;DR: Although recent advances in the treatment of thalassemia can prolong patient life spans, problems may arise when patients are transferred from pediatric health care settings to adult health care sets, and recommendations for handling them are discussed.
Abstract: Thalassemia is a chronic condition that presents a range of clinical and psychosocial challenges. Although recent advances in the treatment of thalassemia can prolong patient life spans, problems may arise when patients are transferred from pediatric health care settings to adult health care settings. These issues and our recommendations for handling them are discussed.
TL;DR: The possible role of GH–IGF‐I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease is studied.
Abstract: Summary
Background and objective GH and IGF-I exert an important role in the control of bone formation, as shown by decreased bone mineral density and increased fracture risk in adult hypopituitary patients untreated for GH deficiency (GHD). Different degrees of bone demineralization are frequently reported in patients affected by β-thalassaemia. Considering the high prevalence of GHD recently observed by our group among adult thalassaemic patients, we elected to study the possible role of GH–IGF-I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease.
Design Sixty-four adult thalassaemic patients (49 with thalassaemia major and 15 with thalassaemia intermedia, 23 men and 41 women, aged 31·4 ± 6·8 years) were studied.
Methods Bone mineral density was assessed by dual energy X-ray absorptiometry at lumbar spine in 62 patients and at proximal femur in 58. All patients underwent GHRH (1 µg/kg as an i.v. bolus) plus arginine (0·5 g/kg as a 30-min i.v. infusion) testing. Severe GHD was defined by GH peaks < 9 µg/l, whereas partial GHD was defined by GH peaks ranging from 9 to 16·5 µg/l. Blood samples for IGF-I measurement were collected.
Results Lumbar osteoporosis and osteopenia were demonstrated in 46/62 (74·1%) and 14/62 (22·5%) patients, respectively. Femoral osteoporosis and osteopenia were documented in 22/58 (37·9%) and 32/58 (55·1%) patients, respectively. Severe GHD was demonstrated in 16/64 patients (25%), while 11 additional patients (17·1%) displayed partial GHD. IGF-I standard deviation score (SDS) was low, that is, below –1·88, in the majority (54·6%) of patients. Lumbar T-score values were not correlated with either GH peaks or IGF-I SDS values. Femoral T-score values were positively correlated with GH peaks (r = 0·38, P < 0·005) and IGF-I SDS values (r = 0·39, P < 0·005). Multiple regression analysis pointed to both GH peak and IGF-I SDS as predictors of femoral T-score. Furthermore, mean femoral T-score was significantly lower in patients with severe GHD than in those with normal GH secretion (–2·94 ± 0·25 vs.–2·15 ± 0·12, P < 0·01).
Conclusion This study, while confirming the high prevalence of both osteopenia/osteoporosis and somatotropin–somatomedin deficiency in adult thalassaemic patients, indicates that defective GH secretion and diminished serum IGF-I levels may contribute to femoral demineralization in these patients. Further studies are worth carrying out to evaluate the efficacy of biosynthetic GH administration on bone abnormalities of GH-deficient thalassaemic adults.
TL;DR: The data show that the type of food, caloric content, and fat content of the meal influence the bioavailability of deferasirox when consumed concomitantly, but this is not the case when defer asirox is administered at least 30 minutes before a meal.
Abstract: Deferasirox (ICL670) is representative of a new class of tridentate iron chelators, formulated as tablets for dispersion. Deferasirox has exhibited high potency and a clinically manageable safety profile in preclinical models and in an extensive clinical program. The effect of food and time of food intake on the pharmacokinetics of deferasirox was investigated in healthy volunteers and patients with transfusional hemosiderosis. The bioequivalence of a single oral dose of deferasirox (20 mg/kg) was assessed following administration either before a high-fat or standard breakfast or concurrent with a standard breakfast in comparison with fasted conditions in healthy volunteers. The bioavailability of deferasirox was determined following a single oral dose (20 mg/kg) under fed and fasted conditions in patients. These data show that the type of food, caloric content, and fat content of the meal influence the bioavailability of deferasirox when consumed concomitantly. In contrast, this is not the case when deferasirox is administered at least 30 minutes before a meal. In conclusion, it is recommended that deferasirox be administered at least 30 minutes prior to meals. When this is not feasible, deferasirox should be administered consistently at the same time before meals to limit the sources of variability that affect absorption.
TL;DR: Deferasirox is a new, convenient, once-daily oral iron chelator that has demonstrated in various clinical trials good efficacy and acceptable safety profile in adult and pediatric patients affected by transfusion-dependent thalassemia major and by different chronic anemias.
Abstract: Although blood transfusions are important for patients with hemoglobinopathies, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Desferrioxamine (DFO) is the reference-standard iron chelator whose safety and efficacy profile has been established through many years of clinical use. DFO side effects are acceptable and manageable however the prolonged subcutaneous infusion regimen of 5-7 days per week is very demanding and results in poor adherence to therapy. Deferiprone (Ferriprox, L1) is a bidentate molecule, orally administrable three-times/day, licensed in Europe and in other regions but in the USA and Canada, for the treatment of iron overload in patients for whom DFO therapy is contraindicated or inadequate. Preliminary evidences suggest that Deferiprone may be more effective than DFO in chelating cardiac iron. The side effects include gastrointestinal symptoms, liver dysfunction, joint pain, neutropenia and agranulocytosis. A weekly assessment of white blood cell counts is recommended because of the risk of agranulocytosis. Deferasirox is a new, convenient, once-daily oral iron chelator that has demonstrated in various clinical trials good efficacy and acceptable safety profile in adult and pediatric patients affected by transfusion-dependent thalassemia major and by different chronic anemias (SCD, BDA, MDS). The long half-life of Deferasirox (16-18 hours) provides sustained 24 hr iron chelation coverage. The efficacy and safety profile have been evaluated in more than 1000 patients in clinical trials allowing FDA registration. Patient satisfaction with Deferasirox was superior than with DFO therapy.
TL;DR: Intathoracic and symptomatic pelvic EH masses in a 48‐year‐old woman and intrath oracic bilateral masses causing respiratory insufficiency with pleural effusion in a 42‐year-old male, both affected by thalassaemia intermedia are described.
Abstract: Extramedullary haematopoiesis (EH) is the production of blood cell precursors outside the bone marrow that occurs in various disorders, such as thalassaemia, sickle cell anaemia, hereditary spherocytosis, polycythaemia vera, myelofibrosis and other haematological diseases. In chronic anaemia, it is a physiological response to increased erythropoietin. In some other conditions, such as myeloid metaplasia, polycythaemia vera or chronic myeloid leukaemia, EH is due to a clonal disorder of haematopoiesis that enables progenitor cells to escape from the marrow and lodge in other organs. EH usually involves the liver, spleen and lymph nodes or it can be paravertebral, intrathoracic, pelvic. It is often asymptomatic but can sometimes lead to symptomatic tumour-like masses. Treatment options are still controversial and limited, including hypertransfusion regimen, surgical treatment, radiotherapy and hydroxyurea (HU). We describe intrathoracic and symptomatic pelvic EH masses in a 48-year-old woman and intrathoracic bilateral masses causing respiratory insufficiency with pleural effusion in a 42-year-old male, both affected by thalassaemia intermedia. Both patients showed a clinical improvement with hydroxyurea therapy and occasional blood transfusions.
TL;DR: In β-thalassemia pts with myocardial siderosis, deferasirox at a mean dose of 32.6 mg/kg/d over 1 yr removes iron from the heart, associated with maintained ejection fraction and a significant decrease in hepatic and total body iron burden.
TL;DR: An early involvement of left ventricular performance was shown by myocardial performance index in patients with type 2 diabetes of recent onset without coronary artery disease, independently of the hypertension presence and could provide a feasible approach to detect a pre-clinical diabetic cardiomyopathy.
Abstract: To evaluate whether myocardial performance index detects a subclinical impairment of left ventricular systolic and diastolic function in patients with early stage of type 2 diabetes, without coronary artery disease, with or without hypertension. Furthermore, to evaluate whether some echocardiographic parameters relate to the metabolic control. Fourty-five consecutive male patients (mean age 52.5 years) with type 2 diabetes mellitus of recent onset (23 hypertensives and 22 normotensives) and 22 age matched healthy controls males were analysed. All participants had normal exercise ECG. All subjects underwent standard and Doppler echocardiography for the assessment of the isovolumic Doppler time interval and Doppler-derived myocardial performance index. In all diabetic patients a glycated haemoglobin test was also performed. No differences were observed in blood pressure, heart rate, and conventional echocardiographic parameters comparing the 2 subgroups of diabetic patients and the controls. Myocardial performance index was significantly higher in diabetic patients independently of the hypertension occurrence, compared to the controls (0.49 and 0.49 diabetic normotensives and hypertensives respectively vs. 0.39, p < 0.01). Myocardial performance index correlated to glycated haemoglobin significantly (r = 0.37, p < 0.01) in both diabetic subgroups. Thus, an early involvement of left ventricular performance was shown by myocardial performance index in patients with type 2 diabetes of recent onset without coronary artery disease, independently of the hypertension presence. These abnormalities can provide a feasible approach to detect a pre-clinical diabetic cardiomyopathy and could be useful for an indirect assessment of the metabolic control.
TL;DR: The results from this 1-yr study confirm the ability of once-daily deferasirox to provide sustained reduction in toxic LPI levels across various transfusion-dependent anemias, supporting previous data in pts with β-thalassemia.
TL;DR: A probabilistic approach is needed to determine the carrier and removal status of canine coronavirus, which has been implicated in the spread of infectious disease in animals.
Abstract: KARIMI M, 2007, AM J HEMATOL 0815; Taher A, 2006, THROMB HAEMOSTASIS, V96, P488, DOI 10.1160-TH06-05-0267
TL;DR: Aessopos et al. as mentioned in this paper, 2005, CHEST, V127, P1523, DOI 10.1378-chest.5.1.02376.
Abstract: Aessopos A, 2005, CHEST, V127, P1523, DOI 10.1378-chest.127.5.1523; Aessopos A, 2001, BLOOD, V97, P3411, DOI 10.1182-blood.V97.11.3411; CAPELLINI MD, 2002, HEMATOL J, V65; CAPELLINI MD, 2007, GUIDELINES CLIN MANA, pCH11; Cappellini MD, 2005, SEMIN HEMATOL, V42, pS19, DOI 10.1053-j.seminhematol.2005.01.001; Cappellini MD, 2000, BRIT J HAEMATOL, V111, P467, DOI 10.1046-j.1365-2141.2000.02376.x; Castelli R, 2004, AM J MED SCI, V328, P299, DOI 10.1097-00000441-200411000-00012; Chehal Aref, 2003, Spine (Phila Pa 1976), V28, pE245, DOI 10.1097-00007632-200307010-00024; Dixit A, 2005, ANN HEMATOL, V84, P441, DOI 10.1007-s00277-005-1026-4; Eldor A, 2002, BLOOD, V99, P36, DOI 10.1182-blood.V99.1.36; GIMMON Z, 1982, PLAST RECONSTR SURG, V69, P320, DOI 10.1097-00006534-198202000-00023; Karimi M, 2005, J PEDIAT HEMATOL ONC, V27, P380, DOI 10.1097-01.mph.0000174386.13109.28; Kushner J P, 2001, Hematology Am Soc Hematol Educ Program, P47; Mourad FH, 2003, BRIT J HAEMATOL, V121, P187, DOI 10.1046-j.1365-2141.2003.04240.x; Origa R, 2005, ANN NY ACAD SCI, V1054, P451, DOI 10.1196-annals.1345.051; PERRINE SP, 1993, NEW ENGL J MED, V328, P81, DOI 10.1056-NEJM199301143280202; St Pierre TG, 2005, BLOOD, V105, P855, DOI 10.1182-blood-2004-01-0177; Taher A, 2006, THROMB HAEMOSTASIS, V96, P488, DOI 10.1160-TH06-05-0267; TAHER A, 2006, BLOOD CELL MOL DIS, V27, P12; TAHER A, 2007, ASH ANN M, V110, P3818; Weatherall DJ, 2001, J HEMATOL S1, V86, P186
TL;DR: This analysis evaluates efficacy and safety during up to 4.5 years of deferasirox treatment in adult and pediatric patients with β-thalassemia, finding a dose-dependent reduction in patients’ liver function was generally well-reported and there were no changes in liver function over that period.
TL;DR: In this article, the ethical issues and risks/benefits of current iron chelation therapies were discussed and a paper was published, in the author's opinion, describing the ethical risks and benefits of chelation.
Abstract: Dear Sir,A paper recently published in this journal described, in the author's opinion, the ethical issues and risks/benefits of current iron chelation therapies ([1]). The paper purports to be pro...
TL;DR: This analysis evaluates the safety of deferasirox (Exjade®) in a cohort of adult and pediatric patients with transfusion-dependent anemias and iron overload from two large clinical trials who were chelated to SF levels <1000 ng/mL.
TL;DR: A large, single arm, multicenter, 1-year open-label trial to assess the efficacy and safety of deferasirox in pts with transfusion-dependent iron overload, β-thalassemia and MDS, finding no statistically significant differences in mean change scores for the perceived effectiveness of ICT domain were found.
TL;DR: RNA analysis demonstrated that the lack of the entire promoter prevents the expression of the mutated allele, in fact the Expression of the Ferrochelatase gene was decreased by half in the subjects carrying only the mutation compared to control.
Abstract: Erythropoietic protoporphyria (EPP, MIM 177000) is an autosomal dominant disease with incomplete penetrance since the phenotypic expression requires coinheritance of a null allele and a wild-type low expressed allele of Ferrochelatase gene (FECH). In this study, we identify a peculiar mutation in a young Canadian patient of Italian origin. The patient had clinical and biochemical symptoms of EPP, the wild-type low expressed allele but at preliminary analysis no mutation in the promoter, in the entire coding region and in the splice junctions of the gene. Family studies of seven most common polymorphisms along the gene established absence of Mendelian segregation for the promoter polymorphism only. The intron 1 polymorphism appeared in heterozygosis suggesting an hypothetical deletion in the first region of the gene. In order to identify the size of this deletion, single nucleotide polymorphisms (SNPs) analysis was extended to the upstream N-asparaginyl-tRNA synthetase gene (NARS). We analyzed two polymorphisms in the last exon of this gene and a dizigous region was found in the patient. A Long-PCR with primers located in previously fixed heterozygous regions showed a 10,376 bp deletion (c.1-7887_67+2422del) that included a portion of the upstream intergenic region, the promoter, the exon 1 and a portion of intron 1. RNA analysis demonstrated that the lack of the entire promoter prevents the expression of the mutated allele, in fact the expression of the Ferrochelatase gene was decreased by half in the subjects carrying only the mutation compared to control.
TL;DR: The efficacy and safety of fixed starting doses of deferasirox based on transfusion history, with subsequent dose titration based on serum ferritin (SF) trends were evaluated in the largest ever EPIC trial for an iron chelator.
TL;DR: Cappellini et al. as mentioned in this paper proposed a method to detect the presence of cancer cells in the blood and showed that the method can be used to detect cancer cells from the blood.
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TL;DR: Over a 1-year treatment period, deferasirox significantly reduced iron burden in transfusion-dependent DBA patients with iron overload, suggesting the need to individually titrate the dose according to the rate of iron intake from ongoing blood transfusions, as well as current iron burden and target SF levels.
TL;DR: These data confirm that in heavily iron-loaded pts with β-thalassemia major, higher deferasirox doses are needed to achieve significant reductions in SF, while lower doses are able to maintain safety balance.