6533b7cffe1ef96bd1258688
RESEARCH PRODUCT
Improving survival with deferiprone treatment in patients with thalassemia major: A prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies
Michele RizzoCrocetta ArgentoAngela VitranoPietro VioliR. MaliziaDomenico Giuseppe D'ascolaCarmelo MagnanoAurelio MaggioMarcello CapraSaveria CampisiFrancesco CantellaFrancesca Valeria CommendatoreFrancesco GagliardottoLiana CucciaGiovanni GiugnoRocca CingariCarmelo FidoneMaria Antonietta RomeoPaolo RiganoLuciano ProssomaritiAnna MeoPaolo CianciulliGaetano RoccamoAldo FilosaMaria Concetta GalatiGaetano GiuffridaVincenzo CarusoTuri LombardoAngela CiancioCalogera Gerardisubject
MaleThalassemiaKaplan-Meier Estimatelaw.inventionchemistry.chemical_compoundRandomized controlled triallawCause of DeathNeoplasmsDeferiproneProspective StudiesChildCause of deathHazard ratioHematologyMiddle AgedCombined Modality TherapySurvival RateThalassemia survival chelation treatment trial thalassemia majorCombinationSplenectomyMolecular MedicineDrug Therapy CombinationFemaleDeferiproneAdultmedicine.medical_specialtyAdolescentPyridonesDeferoxamineIron Chelating AgentsYoung AdultDrug TherapyInternal medicinemedicineHumansBlood TransfusionAdolescent; Adult; Blood Transfusion; Cause of Death; Chelation Therapy; Child; Combined Modality Therapy; Deferoxamine; Drug Therapy; Combination; Female; Heart Failure; Humans; Iron Chelating Agents; Kaplan-Meiers Estimate; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prospective Studies; Pyridones; Splenectomy; Survival Rate; Young Adult; beta-ThalassemiaMolecular BiologySurvival rateKaplan-Meiers EstimateSurvival analysisProportional Hazards ModelsHeart Failurebusiness.industryProportional hazards modelbeta-ThalassemiaCell Biologymedicine.diseaseChelation TherapySurgerychemistrybusinessdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-01-01 |