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1.
Br J Haematol ; 176(1): 124-130, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27748513

RESUMO

In the last few decades, the life expectancy of regularly transfused ß-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with ß-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P < 0·0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0·086), reducing the Hazard Ratio of death in TM compared to TI from 6·8 [95% confidence interval (CI) 2·6-17·5] before 1965 to 2·8 (95% CI 0·8-9·2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.


Assuntos
Expectativa de Vida , Talassemia beta/classificação , Talassemia beta/mortalidade , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem , Talassemia beta/epidemiologia , Talassemia beta/terapia
2.
Blood Cells Mol Dis ; 51(2): 85-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23628348

RESUMO

Transfusion and iron chelation treatment have significantly reduced morbidity and improved survival of patients with thalassemia major. However, cardiac disease continues to be the most common cause of death. We report the left-ventricular ejection fraction, determined by echocardiography, in one hundred sixty-eight patients with thalassemia major followed for at least 5years who received continuous monotherapy with deferoxamine (N=108) or deferiprone (N=60). The statistical analysis, using the generalized estimating equations model, indicated that the group treated with deferiprone had a significantly better left-ventricular ejection fraction than did those treated with deferoxamine (coefficient 0.97; 95% CI 0.37; 1.6, p=0.002). The heart may be particularly sensitive to iron-induced mitochondrial damage because of the large number of mitochondria and its low level of antioxidants. Deferiprone, because of its lower molecular weight, might cross into heart mitochondria more efficiently, improving their activity and, thereby, myocardial cell function. Our findings indicate that the long-term administration of deferiprone significantly enhances left-ventricular function over time in comparison with deferoxamine treatment. However, because of limitations related to the design of this study, these findings should be confirmed in a prospective, randomized clinical trial.


Assuntos
Desferroxamina/uso terapêutico , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Piridonas/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Talassemia beta/complicações , Adulto , Deferiprona , Feminino , Cardiopatias/tratamento farmacológico , Humanos , Quelantes de Ferro/uso terapêutico , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
3.
Blood ; 116(16): 2875-83, 2010 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-20551378

RESUMO

Chelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus- or hepatitis C virus-related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Talassemia/complicações , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/transmissão , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/transmissão , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Talassemia/tratamento farmacológico , Talassemia/epidemiologia
4.
Am J Hematol ; 87(7): 732-3, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22622672
5.
Hemoglobin ; 35(3): 206-16, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21599433

RESUMO

In ß-thalassemia major (ß-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO vs. L1 alone iron chelation therapy in ß-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during a 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin level was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients (p = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences (log-rank test, p = 0.3145). Adverse events and costs were comparable between the groups. Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone, without significant differences of survival, adverse events or costs. These findings were confirmed in a further 21-month follow-up. These data suggest that alternating sequential L1-DFO treatment may be useful for some ß-TM patients who may not be able to receive other forms of chelation treatment.


Assuntos
Desferroxamina/administração & dosagem , Piridonas/administração & dosagem , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Terapia por Quelação/métodos , Deferiprona , Desferroxamina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Quelantes de Ferro/uso terapêutico , Masculino , Piridonas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
6.
Br J Haematol ; 148(3): 476-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19930183

RESUMO

The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-beta-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0.70; P > 0.001) independently of liver iron concentration (r = 0.01; P = 0.932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0.997 (95% confidence interval [CI]: 0.925-1.000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69.0-100.0) and 95% specificity (95% CI: 84.2-99.3). Transient elastography is a reliable non-invasive tool for diagnosing advanced liver fibrosis in homozygous-beta-thalassaemics, regardless of the degree of iron overload.


Assuntos
Sobrecarga de Ferro/complicações , Cirrose Hepática/diagnóstico por imagem , Talassemia beta/complicações , Adulto , Biópsia , Criança , Técnicas de Imagem por Elasticidade/métodos , Métodos Epidemiológicos , Feminino , Hepatite C Crônica/complicações , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Clin Drug Investig ; 30(4): 267-73, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20225910

RESUMO

We report the long-term effects of deferasirox 10-30 mg/kg/day on cardiac iron overload in a case series of five patients with transfusion-dependent beta-thalassaemia major who underwent up to 5 years of chelation therapy. Iron overload was monitored by multislice multi-echo T2* magnetic resonance imaging (MRI). Overall, T2* MRI showed a decrease from baseline in cardiac iron levels in all patients during treatment with deferasirox (baseline T2* levels 13-24 ms; final T2* levels 21-41 ms). The improvement in T2* values correlated with maintenance of left ventricular ejection fraction (LVEF) [baseline LVEF values 56-61%; final LVEF values 57-70%]. Deferasirox chelation treatment regimen was well tolerated and adherence to the regimen was good. In conclusion, this case series suggests that deferasirox may decrease cardiac iron overload and maintain stable LVEF over the long term. Moreover, it emphasizes the importance of T2* multislice multi-echo MRI in the monitoring of cardiac iron overload.


Assuntos
Benzoatos/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Triazóis/uso terapêutico , Adolescente , Adulto , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Transfusão de Sangue/métodos , Criança , Deferasirox , Relação Dose-Resposta a Droga , Feminino , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/etiologia , Masculino , Miocárdio/patologia , Fatores de Tempo , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/terapia
8.
Br J Haematol ; 145(2): 245-54, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19236376

RESUMO

A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these were randomized and underwent intention-to-treat analysis. The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP-DFO patients compared with DFP-alone patients (P = 0.005). Kaplan-Meier survival analysis for the two chelation treatments did not show any statistically significant differences (long-rank test, P = 0.3145). Adverse events and costs were comparable between the groups. The trial results show that sequential DFP-DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival, adverse events, or costs.


Assuntos
Desferroxamina/administração & dosagem , Quelantes de Ferro/administração & dosagem , Piridonas/administração & dosagem , Talassemia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Deferiprona , Desferroxamina/uso terapêutico , Quimioterapia Combinada , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Infusões Subcutâneas , Quelantes de Ferro/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Piridonas/uso terapêutico , Talassemia/sangue , Talassemia/mortalidade , Resultado do Tratamento , Adulto Jovem
9.
Blood Cells Mol Dis ; 42(3): 247-51, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19233692

RESUMO

The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone-deferoxamine (DFP-DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared deferoxamine (DFO) versus DFP alone, sequential DFP-DFO, or combined DFP-DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP-DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP-DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant (p-value<0.013). For each increasing year of age, the hazard ratio for males was 1.03 higher than that for females (p-value<0.013). In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are deferoxamine-treatment, complications, and the interaction effect of sex and age.


Assuntos
Terapia por Quelação , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Transfusão de Sangue , Causas de Morte , Criança , Terapia Combinada , Deferiprona , Desferroxamina/administração & dosagem , Desferroxamina/uso terapêutico , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Humanos , Quelantes de Ferro/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Piridonas/administração & dosagem , Esplenectomia , Taxa de Sobrevida , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/mortalidade , Talassemia beta/terapia
10.
Haematologica ; 93(8): 1243-6, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18556410

RESUMO

Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liver fibrosis, while hepatitis virus C-RNA positive patients infected with genotype 1 or 4 and iron overload more frequently developed advanced fibrosis. Hepatitis virus C infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Adequate chelation therapy usually prevents the development of liver fibrosis in thalassemics free of hepatitis virus C-infection and reduces the risk of developing severe fibrosis in thalassemics with chronic hepatitis C.


Assuntos
Hepatite C Crônica/complicações , Sobrecarga de Ferro/complicações , Talassemia/etiologia , Reação Transfusional , Adolescente , Adulto , Biópsia , Estudos de Coortes , Feminino , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C Crônica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Estudos Retrospectivos , Esplenectomia , Talassemia/sangue , Carga Viral
11.
J Cardiovasc Med (Hagerstown) ; 16(10): 689-95, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26090920

RESUMO

AIMS: Our aim was to evaluate the correlation between myocardial fibrosis detected using the late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) technique and chronic hepatitis C (CHC) in a large, retrospective, multicentre cohort of thalassemia major patients. METHODS: LGE images were acquired in 434 thalassemia major patients (233 men, 31 ±â€Š9 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) study. Hepatitis C virus (HCV)-RNA tests were sensitive to detect more than 50  copies/ml. RESULTS: No patient manifested moderate/severe adverse events associated with the use of Gadobutrol. Myocardial fibrosis was detected in 90 (21%) patients. Among the 312 patients tested for HCV-RNA, there was a significant correlation between the presence of myocardial fibrosis and CHC (P = 0.011). Among the 62 patients with myocardial fibrosis tested for HCV-RNA, we found a significantly higher prevalence of diabetes mellitus in CHC patients versus the no-CHC patients (P = 0.049). CONCLUSION: Our findings support the use of the LGE CMR approach well tolerated in the thalassemia major patients with CHC. HCV infection can be involved in the pathogenesis of myocardial fibrosis through both myocarditis directly and the pancreas and liver damage with the development of diabetes indirectly. These patients could therefore benefit from cardioactive drugs and therapeutic interventions directed towards the eradication of virus.


Assuntos
Fibrose Endomiocárdica/diagnóstico , Gadolínio/análise , Hepatite C Crônica/complicações , Imagem Cinética por Ressonância Magnética/efeitos adversos , Talassemia/complicações , Adulto , Meios de Contraste , Estudos Transversais , Diabetes Mellitus/diagnóstico , Feminino , Coração/fisiopatologia , Hepacivirus/genética , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
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