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1.
Radiol Med ; 127(11): 1199-1208, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36087241

RESUMO

PURPOSE: We evaluated the feasibility and reproducibility of bone marrow T2* values and established the lower limit of normal in a cohort of healthy subjects. We investigated the clinical correlates of bone marrow T2* values in patients with thalassemia major (TM). MATERIAL AND METHODS: Thirty healthy subjects and 274 consecutive TM patients (38.96 ± 8.49 years, 151 females) underwent MRI at 1.5T. An axial slice in the upper abdomen was acquired by a T2* gradient-echo multiecho sequence and the T2* value was calculated in a circular region of interest defined in the visible body of the first or second lumbar vertebra. In patients, also liver and heart T2* values were assessed. RESULTS: In healthy subjects bone marrow T2* values were independent of age and gender. The lower limit of normal for bone marrow T2* was 13 ms. In both healthy subjects and 30 randomly selected patients, the coefficient of variation for inter-operator-reproducibility was < 10%. TM patients exhibited significantly lower bone marrow T2* values than healthy subjects (7.47 ± 5.18 ms vs. 17.08 ± 1.89 ms; p < 0.0001). A pathological bone marrow T2* was detected in 82.8% of TM patients. In TM, the female sex was associated with reduced bone marrow T2* values. Bone marrow T2* values were inversely correlated with mean serum ferritin levels (R = -0.431; P < 0.0001) and hepatic iron load (R = - 0.215; P < 0.0001). A serum ferritin level > 536 ng/ml predicted the presence of a pathological bone marrow T2*. A positive correlation was found between bone marrow and heart T2* values (R = 0.143; P = 0.018). A normal bone marrow T2* showed a negative predictive value of 100% for cardiac iron. CONCLUSION: Bone marrow T2* measurements can be easily obtained using the same sequences acquired for liver iron quantification and may bring new insights into the pathophysiology of iron deposition; hence, they should be incorporated into clinical practice.


Assuntos
Sobrecarga de Ferro , Talassemia beta , Feminino , Humanos , Talassemia beta/diagnóstico por imagem , Talassemia beta/complicações , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Ferritinas , Ferro , Sobrecarga de Ferro/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética , Miocárdio/patologia , Valores de Referência , Reprodutibilidade dos Testes , Estudos de Casos e Controles
2.
Lancet Haematol ; 7(6): e469-e478, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32470438

RESUMO

BACKGROUND: Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox. METHODS: DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (<100 mg/kg per day) or deferasirox (<40 mg/kg per day; deferasirox is not registered for use in children aged <2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (<10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged >10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512. FINDINGS: 435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had ß-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group. INTERPRETATION: In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. FUNDING: EU Seventh Framework Programme.


Assuntos
Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Transfusão de Eritrócitos/métodos , Hemoglobinopatias/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Administração Oral , Adolescente , Agranulocitose/induzido quimicamente , Agranulocitose/epidemiologia , Albânia/epidemiologia , Anemia Falciforme/terapia , Técnicas de Imagem Cardíaca/métodos , Criança , Pré-Escolar , Chipre/epidemiologia , Deferasirox/administração & dosagem , Deferasirox/economia , Deferiprona/administração & dosagem , Deferiprona/economia , Egito/epidemiologia , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Ferritinas/sangue , Ferritinas/efeitos dos fármacos , Grécia/epidemiologia , Hemoglobinopatias/terapia , Humanos , Lactente , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/economia , Sobrecarga de Ferro/sangue , Itália/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Cooperação do Paciente , Resultado do Tratamento , Tunísia/epidemiologia , Reino Unido/epidemiologia , Doenças Urológicas/induzido quimicamente , Doenças Urológicas/epidemiologia , Talassemia beta/terapia
3.
Clin Drug Investig ; 37(5): 453-464, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28185140

RESUMO

PURPOSE: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. METHODS: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY. RESULTS: In all scenarios modelled, DFP was the dominant treatment strategy. Sensitivity analyses showed that DFP dominated the other treatments with a >99% likelihood of being cost-effective against DFX and DFO at a willingness to pay threshold of €20,000 per QALY. CONCLUSIONS: DFP was the dominant and most cost-effective treatment for managing chronic iron overload in TM patients. Its use can result in substantial cost savings for the Italian healthcare system.


Assuntos
Análise Custo-Benefício/métodos , Custos de Cuidados de Saúde , Quelantes de Ferro/economia , Talassemia beta/tratamento farmacológico , Talassemia beta/economia , Benzoatos/administração & dosagem , Benzoatos/economia , Estudos de Coortes , Deferasirox , Deferiprona , Desferroxamina/administração & dosagem , Desferroxamina/economia , Vias de Administração de Medicamentos , Humanos , Quelantes de Ferro/administração & dosagem , Itália/epidemiologia , Piridonas/administração & dosagem , Piridonas/economia , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/economia , Talassemia beta/epidemiologia
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