RESUMO
A multicenter randomized open-label long-term sequential deferipronedeferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].
Assuntos
Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Quelantes de Ferro/efeitos adversos , Piridonas/uso terapêutico , Talassemia beta/tratamento farmacológico , Talassemia beta/fisiopatologia , Adulto , Deferiprona , Desferroxamina/administração & dosagem , Desferroxamina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Quelantes de Ferro/administração & dosagem , Masculino , Modelos Biológicos , Piridonas/administração & dosagem , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , UltrassonografiaRESUMO
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 JovemRESUMO
Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of ß-thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short- (1 year) and long-term (mean follow-up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo. Our results confirm a good response to HC after a short-term follow-up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow-up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long-term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the 'in vivo' response. The mechanism of this loss of response to HC remains to be determined.