ALBERT

Description: Background Cardiac iron removal is relatively slow and patients with cardiac siderosis can take years to normalize cardiac T2* to 〉20 ms. Prospective comparison of iron chelators are mostly limited to studies of 1-yr duration. CORDELIA is a large randomized trial comparing deferasirox (DFX) with deferoxamine (DFO) in patients with β-thalassemia major (TM), which demonstrated the non-inferiority of DFX vs DFO for cardiac iron removal at 1 yr, with a trend for superiority of DFX (P=0.057). This 1-yr extension was planned to collect additional data on efficacy and safety of DFX and DFO in patients with cardiac siderosis when treated for up to 2 yr. Methods Study design has been reported previously (Pennell Blood 2012; abst 2124). Patients enrolled had cardiovascular magnetic resonance-measured cardiac T2* 6–20 ms, left ventricular ejection fraction (LVEF) ≥56%, and R2-magnetic resonance imaging liver iron concentration (LIC) ≥3 mg Fe/g dw. Patients completing 1 yr were eligible to continue on DFX or DFO as assigned, or to switch treatment on entering the extension if judged by the investigator to be of therapeutic benefit. Target doses were an intensified DFO regimen of 50–60 mg/kg/d sc for 8–12 h, 5–7 d/wk, or DFX at 40 mg/kg/d. Efficacy is reported for changes from core baseline (BL). Safety was monitored continuously. Results for patients continuing with DFX or DFO are reported here. Results In total, 160/197 patients completed 1 yr; 74 patients continued into the extension on DFX (mean age 20.1 ± 6.9 yr; 59.5% male) and 29 patients on DFO (17.0 ± 5.4 yr; 58.6%). At core BL, 29.7% DFX patients had cardiac T2* 33% from BL and 〉 upper limit of normal (ULN) at 2 consecutive values occurred in 2.7% of DFX and 3.4% of DFO patients. Frequency of ALT elevations 〉5 x ULN and 2 x BL were comparable between groups. Discussion Cardiac T2* increased substantially during 2-yr treatment with DFX or DFO. Improvement with DFX was comparable with DFO, although DFO patient numbers were low. The magnitude of cardiac T2* improvement with DFX was consistent with previous long-term studies (Pennell Blood 2010). Mean LVEF was stable and remained within normal limits in both groups. LIC continued to decrease from very high BL levels with DFX and DFO. The reduction in CIC in the extension was similar or possibly greater than in the core, which might relate to the falling LIC. Long-term safety profiles of DFX and DFO were consistent with previous reports. Disclosures: Pennell: Shire: Consultancy, Honoraria; ApoPharma: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Porter:Celgene: Consultancy; Shire: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Piga:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Wegener:Novartis: Employment. Habr:Novartis: Employment. Shen:Novartis: Employment. Aydinok:Shire: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: The management cost of iron overload is rising with the introduction of magnetic resonance T2-star (T2*), oral iron chelation and combination therapy. The aim of this study was to develop and validate a simple and cheap clinical risk assessment model that would predict cardiac disease risk among patients with thalassemia major. The data of patients (254, aged 〉 15 years) with b-thalassemia major, who had been chronically transfused at Dubai Thalassemia Center from 2007 to 2011, were used to develop the model. Gathered data included data related to cardiac disease, T2*, and six other clinical and biochemical parameters known to be associated with an increased risk of cardiac siderosis. The parameters were: age, sex, serum ferritin, diabetes, hypogonadism, and splenectomy. Cardiac disease patients were defined as patients (living or dead) who developed cardiac failure or arrhythmias during the study period. Data was analyzed using SPSS version 20. The predictive model was developed using logistic regression analysis. Thalassemia patients who developed cardiac disease were used as the outcome measure. All parameters were included in the model. A weighted scoring system was obtained by rounding down odds ratios to the nearest integer. Model validity analysis was performed on patients with available T2* data (102). Several standard validation measures were computed including sensitivity, specificity, positive predictive value (PPV), the receiver operating characteristic (ROC) curve and the Youden Index. Several model cutoffs were tested until the model delivered the best prediction outcome. A total of 254 thalassemia major patients were studied. The mean age was 23.3 years ± 5.4 (49% were female and 51% were male). Sixteen (6.3%) patients experienced cardiac disease, 55 (21.7%) had hypogonadism, 51 (21%) had diabetes and 29 (11.4%) had undergone splenectomy. Cardiac disease was found to be significantly associated with age 〉 22 years (p=0.004), hypogonadism (p=0.000), splenectomy (p=0.002) and diabetes (p=0.000). While the association of gender and serum ferritin with cardiac disease was not significant (p= 0.146, p=0.158). The model delivered the best prediction outcome at a T2*value ≤ 20 and a model score cutoff ≥ 8 with a sensitivity of 80%, a specificity of 45%, a PPV of 57% and an NPV of 71%. Among the 102 patients with available T2* data, all cardiac disease patients were equally identified by a T2*value ≤20 and by the newly developed model. The model defined 38% of the patients as high risk, which is lower but close to the value (48%) determined by the T2*value ≤20. In the present study, we developed and validated a clinical risk prediction model for cardiac siderosis by using patients (aged 〉15 years) with thalassemia major at Dubai Thalassemia Centre as the study population. The model is easy to use by health care providers and compares well with the predictions determined from T2* data. The fact that this model was developed using data from patients who were mostly of Asian ethnic origin should make it useful in areas where there is a high risk of cardiac siderosis and limited resources. The current study has some limitations, including its retrospective study design, the relatively low event rate and the lack of T2* data for all of the studied population. The impact of this model for predicting clinical outcomes needs to be further assessed by evaluating other variables before it can be applied in clinical setup. Disclosures: No relevant conflicts of interest to declare.

Description: Key Points In β-thalassemia major patients with severe iron burden, deferasirox was noninferior to deferoxamine for myocardial iron removal. The ejection fraction was stable during treatment for both deferasirox and deferoxamine.

Description: Abstract 2069 Introduction: Mechanisms leading to pulmonary hypertension (PHT) in patients with thalassemia intermedia (TI) are still controversial. Moreover, clinical and laboratory characteristics of patients who eventually develop PHT have not been identified. Our aim was to identify factors that characterize TI patients who develop PHT. Methods: Data was retrospectively retrieved from the Thalassemia Intermedia Registry, a database of 584 TI patients currently registered at six comprehensive care centers in Lebanon, Italy, Iran, Egypt, United Arab Emirates, and Oman. Institutional review boards at each center approved the study protocol. Two Groups of patients were identified: Group I, TI patients with documented PHT (n=64; mean age 37.3 ± 10.6; 44% males); and Group II, age- and sex-matched TI patients without PHT (n=64; mean age 37.9 ± 11.4; 44% males). Collected data included demographics, laboratory parameters, disease-complications, and received treatments that may influence PHT development and reflected the period prior to PHT occurrence. Results: There were no statistically significant differences in mean platelet counts, total or fetal hemoglobin levels between the two Groups. However, mean serum ferritin level was higher in Group I compared to Group II (1233.2 ± 499.2 vs. 654.7 ± 234.5 ng/ml; P=0.01). Moreover, mean nucleated red blood cell (NRBC) count was higher in Group I compared to Group II (354.2 ± 199.2 vs. 214.7 ± 94.5 ×10⋀6/l; P=0.03). A higher proportion of patients were splenectomized (84.4% vs. 46.9%; P

Description: Despite recent advances in understanding the pathophysiologic mechanisms behind the thalassemia intermedia (TI) phenotype, data on the effects of treatment are deficient. To provide such data, we evaluated 584 TI patients for the associations between patient and disease characteristics, treatment received, and the rate of complications. The most common disease-related complications were osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes mellitus were less frequently observed. On multivariate analysis, older age and splenectomy were independently associated with an increased risk of most disease-related complications. Transfusion therapy was protective for thrombosis, EMH, PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy was associated with an increased risk of endocrinopathy. Iron chelation therapy was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was associated with an increased risk of hypogonadism yet was protective for EMH, PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to the impact of age on complications in TI, and the beneficial role of splenectomy deserves revisiting. This study provides evidence that calls for prospective evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy in TI patients.