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A retrospective magnetic resonance imaging (MRI) study on a large cohort of children with thalassemia major (TM) showed cardiac involvement by early childhood; 21% of children presented with abnormal cardiac T2* and 16% with cardiac fibrosis. Moreover, moderate and/or severe liver iron overload (IO

Although the possibility of asymptomatic course for COVID‐19 infection in splenectomized thalassemia beta major patients is present, screening them for COVID‐19 is important as the progression is still not clear.

In this cross-sectional study we assessed the vascular alterations in retinal and choriocapillaris perfusion in patients affected by β-thalassemia, by means of optical coherence tomography angiography (OCTA). A total of 124 eyes of 62 patients (mean age 44.74 ± 5.79 years old) affected by β-thalassemia (transfusion dependent thalassemia (TDT), non-transfusion dependent thalassemia (NTDT) and minor) were compared to 40 eyes of twenty healthy subjects. We evaluated the vessel density (VD) in superficial capillary plexus, deep capillary plexus, radial peripapillary capillary, choriocapillaris and the foveal avascular zone area. The TDT group showed a statistically significant reduction in retinal and choriocapillaris VD respect to controls and the other groups (p &lt, 0.05). No statistically significant difference was found in OCTA parameters between β-thalassemia minor and controls. The NTDT group showed a significant reduction in VD in deep capillary plexus respect to controls and β-thalassemia minor. Significant negative correlations were shown in TDT group between foveal avascular zone and hemoglobin (r = −0.437, p = 0.044) and between ferritin levels and VD of choriocapillaris (r = −0.431, p = 0.038). The OCTA parameters provided a deeper understanding on retinal and choriocapillaris vascular impairment affected by tissue hypoxia levels and the oxidative stress in different clinical phenotypes of the β-thalassemia.

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.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 aged2 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 aged10 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, NCT01825512.435 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 β-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.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.EU Seventh Framework Programme.

Introduction: Renal dysfunction is a frequent complication in patients suffering from β-thalassemia major (β-TM). The aim of this study was to analyze the renal function and urine metabolomic profile of β-TM patients undergoing transfusions and deferasirox (DFX) therapy, in order to better characterize and shed light on the pathogenesis of renal disease in this setting. Methods and Subjects: 40 patients affected by β-TM treated with DFX and 35 age- and gender-matched healthy controls were enrolled in the study. Renal function was assessed. Glomerular filtration rate (GFR) was estimated with CKD-EPI and Schwartz formula for adults and children, respectively. Renal tubular function and maximal urine concentration ability were tested. Urine specimens were analyzed by nuclear magnetic resonance spectroscopy to identify the urinary metabolite profiles. Results: The study of renal function in β-TM patients revealed normal estimated (e)GFR mean values and the albumin-to-creatinine ratio was Discussion: The major finding of this work is that β-TM patients and controls exhibit different concentrations of some metabolites in the urine. Early recognition of urinary abnormalities may be useful to detect and prevent kidney damage.

This study analysed the impact of liver steatosis (LS) on the parameters of iron overload in 110 patients with non-transfusion dependent thalassaemia (NTDT). LS was diagnosed by ultrasound. Liver iron concentration (LIC) measurements were available for 64 patients who underwent a magnetic resonance imaging (MRI) scan. LS was frequent (35·5%) and was significantly more prevalent in males than in females (49·0% vs. 24·6%, P = 0·008). Patients with LS had significant higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST ratio and ferritin than those without, but LIC values were comparable. An ALT/AST ratio0·89 predicted the presence of LS with a sensitivity of 0·872 and a specificity of 0·901 (P 0·0001). Ferritin levels correlated with LIC values (R = 0·558, P 0·0001) but the correlation was stronger in patients without LS (R = 0·656, P 0·0001) than in patients with LS (R = 0·426, P = 0·05). LS is a frequent issue in NTDT patients and should be suspected in the presence of an ALT/AST ratio0·89. Recently, serum ferritin thresholds that predict clinically relevant LIC for guiding iron chelation therapy when MRI is unavailable have been determined. Our data show that LS may cause increase in ferritin levels and may be responsible for anticipating/exceeding chelation treatment in NTDT patients in the absence of LIC evaluation.

Non-transfusion-dependent thalassemia includes a variety of phenotypes and genotypes that rarely require regular transfusions. However, these patients can experience a wide range of complications. The objective of this retrospective study was to verify whether there is a significant difference in non-transfusion-dependent thalassemia-related complications and treatment among males and females.We performed a re-analysis of samples evaluated in a previously published cross-sectional study, regarding 96 non-transfusion-dependent thalassemia patients followed at the 'UOSD Malattie Rare del Globulo Rosso' Centre of the Cardarelli Hospital in Naples, Italy.We found that females were more anemic than males, but there was no significant difference in prevalence of common complications among genders, except for hypogonadism. Furthermore, the transitory regular transfusions regimen in women who had been pregnant does not seem to have a significant impact on overall prognosis.In non-transfusion-dependent thalassemia patients, the lower levels of hemoglobin found in females do not seem to indicate a higher prevalence of complications.This data should be considered in studies with experimental treatments aiming to correct anemia in patients with non-transfusion-dependent thalassemia. It should probably also be taken into account in order to set up different transfusion regimens among genders in transfusion-dependent patients.

Objectives The liver remains the primary site of iron storage, with liver iron concentration (LIC) being a strong surrogate of total body iron. MRI-R2 can accurately measure LIC. The LICNET (Liver Iron Cutino Network) was established to diagnostics of liver iron overload by MRI-R2 subjects with hemochromatosis in hematological disorders. The aims of the study were to look at variation in LIC measurements during time across different chelation regimens. Methods This was a cross-sectional study of 130 patients attending 9 Italian centers participating in the LICNET. LIC comparisons over time (T0 and T1 ) were made using t test and/or Wilcoxon test. Results LIC significantly decreased from MRI1 to MRI2 although at high variance (median change -0.8 mg Fe/g dw, range: -29.0 to 33.0; P = .011) and 7.7% of patients shifted from LIC values of high risk (>15 mg Fe/g dw) to an intermediate-risk category (7-15 mg Fe/g dw). Median change in LIC and correlation with serum ferritin levels (SF), during different chelation regimens, is reported. Conclusions These findings suggest as longitudinal variation in the LIC is possible, across all chelation regimens. It confirms as SF levels not always can be used for estimating changes in LIC.

Objectives: Despite the correct application of blood transfusions and chelation treatments, beta thalassemia patients have many complications. Systematic population analyses on types and frequency of these complications are very few. The aim of this study is to characterize the complications, their risk factors and their clinical and economic impact. Methods: Complications at baseline and events occurring during one observational year were analyzed in 272 patients aged >12 years. Risk factors were analyzed through chi-squared and unpaired t tests. Logistic regression was applied to perform the risk factors multivariate analysis. Results: A total of 554 complications (1–6 per patient) affected 82.3% of patients. Cardiac complications were less represented than expected. Musculoskeletal diseases were the most represented complications followed by hepatic, sexual and endocrine diseases. Splenectomized patients, born before 1970 and aged >40 years, starting iron chelation therapy when aged >4 years or after receiving more than 20 blood transfusions, presented a significantly higher number of complications. A total of 885 adverse events requiring 34125 additional medical services occurred in 1 year. Of these, 34.9% were related to treatments and 65.1% to other causes. Event numbers, additional medical interventions and cost increased progressively in patients affected by one or more complication compared to patients with no complications. Conclusions: The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.

Background Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect a wide spectrum rather than a dichotomy, and may actually be interchangeable at many parts of the disease journey. Thus, an evaluation of alternate clusters to classify TS patients remains of merit. Aims The aim of this study was to cluster TS patients on the basis of possible clinical indicators of phenotype severity (IPhS) using suitable algorithms and to determine whether these are able to detect cohorts with different clinical phenotypes. Methods Representatives from thirteen international centers from seven countries agreed on 19 IPhS to be collected for a retrospective study. Data from 7910 TS patients were collected. NbClust R Packagewas performed for exploring the existence of a substructure inside the studied TS population, determining the best number of clusters. Unsupervised Random Forest (RF)clustering and the Partitioning Around Medoids (PAM)algorithms were performed to define the clusters. The most important IPhS in defining clusters were selected according to the Gini index. Kaplan-Meier (K-M) survival curves of the identified clusters, defined by the selected IPhS, were used to represent the risk of death for these clusters. Results NbClust method showed the existence of three possible clusters. The RF-PAM procedure defined three distinct clusters with a classification error rate of 4.3% (Fig 1). Moreover, the most important IPhS were patient age, mean serum ferritin level, age at diagnosis, age at first transfusion, age at first iron chelation, and number of complications. K-M curves showed statistically significant differences in survival among the three clusters (p Conclusions The observation of statistically significant differences in survival between the three newly identified clusters but not the original TDT-NTDT classification confirms that the latter classification is interchangeable, and a new triad classification system is required. These findings warrant further evaluation in prospective studies to determine specific thresholds for IPhs indicators that can aid physicians in assigning classes and tailoring care, in order to improve survival in TS patients. Disclosures Meloni: Chiesi Farmaceutici S.p.A.: Other: speakers' honoraria. Pistoia:Chiesi Farmaceutici S.p.A.: Other: speakers' honoraria. Vichinsky:Novartis: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding.

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2*20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.

Background: Classification of phenotype severity in patients with beta-thalassaemia has so far relied mainly on expert opinion using parameters of genotype, clinical features at diagnosis, and transfusion requirement. The aim of this study was to use a large dataset of patients with beta-thalassaemia and evaluate a classification system based on onset variables agreed on by an international expert group, including age at diagnosis, at first transfusion, and at first iron chelation. Methods: A retrospective dataset of 7910 patients with homozygous or compound heterozygous beta-thalassaemia was used and subjected to cluster and classification analysis starting with the onset variables. Results: Cluster analysis suggested that three clusters with minimal overlapping exist. Three phenotype severity classes (mild, moderate, severe) were accordingly assigned which showed statistically significant descending variation of age at diagnosis and start of transfusion and iron chelation. The estimated classification error rate was only 3.07% with an accuracy of 96.93%. It was evident that severe patients had higher blood requirement and iron overload levels and showed a younger age for mortality especially from heart disease. Although mild and moderate patients showed the opposite in gradual severity, they still showed evidence of high morbidity rate for complications that require longer time to manifest (eg liver damage and hepatocellular carcinoma). Conclusion: Age of diagnosis and start of transfusion and iron chelation distinguish three classes of phenotype severity in beta-thalassaemia that carry unique clinical profiles. Further prospective studies are recommended to validate these findings. Funding Statement: The authors state: "None" Declaration of Interests: The authors state: " None to disclose." Ethics Approval Statement: An International Health Repository (IHR) protocol, approved on May 25th, 2017 by the Italian Ethical Committee (EudraCT and Sponsor's Protocol Code Numbers were 2017-004457-17 and 143AOR2017) was established to allow collection of relevant data.

Background Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. Methods We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 β-thalassemia major [TM], 102 β-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. Results The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. Conclusions High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels.

β-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin

Introduction. Despite the increasing of number of patients with Sickle Cell Disease (SCD) in Italy, due to multi-ethnic migratory phenomena, a large percentage of Caucasian sickle population is already present in Italy mainly with b-thal/HbS genotype. Red cell transfusion is one effective treatment for both acute and chronic complications of SCD, while hydroxycarbamide (HC) is used to reduce the frequency of painful vaso-occlusive crises (VOCs) and decrease the need for blood transfusion. Through the National Comprehensive Reference Centers for SCD, the Italian Society of Thalassemia and Hemoglobinopathies (SITE), in collaboration with the Society Italian Transfusion Medicine and Immunohematology (SIMTI) and the Italian Association of Hematology and Pediatric Oncology (AIEOP) conducted a national survey to collect information on different therapeutic approaches used for SCD patients. Aim. To assess therapeutic approaches used a large Italian cohort of patients with SCD, accounting for age, genotype and ethnicity. Patients and Methods. Observational Longitudinal Systemic Multicentre Study (https://clinicaltrials.gov/ct2/show/NCT03397017). Data were collected from 2015 to 2018 through a standard web-based application (www.SITE-italia.org) encrypted by the Central Server. All the SCD patients, treated or not treated, were included in order to identify the overall number and all gave written informed consent. The study was approved by Ethics Committee of Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico of Milan, Italy. Results. Thirty-four centers were involved from 14 Italian regions and 1,579 patients were enrolled (802 male and 777 female; median age 23 years - IQR, 25th-75th 10-41 yrs). Genotype, age and ethnicity distribution are shown in Table 1A. As expected, the median age of non-Caucasian patients, mainly HbSS, is significantly lower than Caucasian ones (p Out of 1,579, 365 SCD patients (23%) did not receive any therapy. Acute transfusion regimen (ATR), Chronic transfusion regimen (CTR) and HC were given in monotherapy, respectively in 160, 226 and 197 patients, or in succession/combination in 631 (Table 1B), distributed throughout genotypes. The main reasons for ATR were acute anemia (384 events) and VOCs (352), followed by acute chest syndrome (ACS; 170), surgery (82), pregnancy (64), splenic sequestration (26), stroke (9); multi-organ failure (MOFs 6) and priapism (5). For CRT, it was acute anemia (306 events) and prevention of VOCs (371), ACS (107), primary stroke prevention (78) and secondary prevention stroke (55), pain HC-resistent (39) and leg ulcers (12). For 275 patients out of 631 it was possible to follow the timing of therapy switching (Table 1C). Of 275 patients, 67.6% switched from ATR/CRT to HC, 2.9% from HC to CRT and 6.5% stopped every therapy. Out of 275 patients, 104 were treated with overlapping therapeutic regimen. Discussion. The significant difference of age in Caucasian and non-Caucasian patients is probably due to the efficacy of the national prevention program of hemoglobinopathies, because the non-Caucasian patients are prevalently born out of Italy. The transfusional approach is similar in HbSS and b°-thal/HbS and b+-thal/HbS patients regarding both ATR and CTR. HbSC genotype needed less therapies(p Summary/Conclusion. The transfusional approach is similar in HbSS, b°-thal/HbS and b+-thal/HbS patients with similar indications, prevalently VOCs and anemia. The significant higher age in Caucasian cohort and the consequent long term follow up could be the cause of variable therapeutic approach observed, however Hydroxycarbamide seemed to be the therapy more frequently used and finally suggested to manage chronic manifestations. Figure. Figure. Disclosures Origa: Apopharma: Honoraria; Novartis: Honoraria; Bluebird Bio: Consultancy; Cerus Corporation: Research Funding. Forni:Apopharma: Other: DSM Board; Celgene: Research Funding; Novartis: Other: travel expenses, Research Funding; Shire: Research Funding; Roche: Consultancy.

Patients with Non-Transfusion-Dependent Thalassemia may require regular transfusion therapy. However, these patients are at risk of developing irregular antibodies, making them untransfusable. Second line treatment usually includes hydroxyurea, which however is not effective in all patients. Other treatment options include thalidomide, which has been reported to be safe and effective in selected patients. We report the case of a patient who experienced improvement of hemoglobin levels and of a part of NTDT related complications, following 36months of continuous therapy with low doses of thalidomide.

Aims Cardiovascular magnetic resonance (CMR) has dramatically changed the clinical practice in thalassemia major (TM), lowering cardiac complications. We prospectively reassessed the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM. Methods and results We considered 481 white TM patients (29.48 ± 8.93 years, 263 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. Mean follow-up was 57.91 ± 18.23 months. After the first CMR scan 69.6% of the patients changed chelation regimen. We recorded 18 episodes of HF. In the multivariate analysis the independent predictive factors were myocardial fibrosis (HR = 10.94, 95% CI = 3.28-36.43, P

We retrospectively evaluated the relationship between serum transferrin receptor-1 (sTfR1) and some fundamental events in the life and the management (the age at diagnosis, the age at the first red blood cells transfusion, the age at splenectomy, and the overall need of chelation therapy) of 111 patients with non-transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities: patients with homozygous or compound heterozygous state for β-thalassemia, patients with triplicated α genotype associated with β heterozygosity, patients with deletional HbH, and patients with the combination of a β defect plus a β chain variant. We found that the group with homozygous or compound heterozygous state for β-thalassemia had the highest sTfR1 levels and that the presence of increased sTfR1 levels (>5 times normal) was associated with a complex and severe history of disease requiring splenectomy, occasional red blood cells transfusions, and early start and continuous iron chelation therapy.The complexity in the management of NTDT patients is an emerging issue due to the wide heterogeneity of clinical behavior. Our data indicate that the measurement of sTfR1 levels, a common laboratory test, could contribute to correctly stratify disease history and the iron chelation strategy in NTDT patients.

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow-up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV.

Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P

Introduction Thalassemia Syndromes (TS) are a group of inherited haemoglobin disorders characterized by different phenotype severity falling among heterozygote state, no transfusion dependent thalassemia (NTDT) and transfusion dependent Thalassemia (TDT) (Graffeo et al, 2018; Taher & Saliba, 2017). Several factors, independently by genotype and globin chain unbalance, modulate the severity of ineffective erythropoiesis (Rivella et al, 2015). Considering the complexity of this pathophysiology, one tool to evaluate patients on an individual basis is needed. The aim of this study was to develop a severity scoring system with a view to initiate timely interventions that would prevent any further complications. Methods An International Health Repository (IHR) protocol was approved on May 25th, 2017 by the Italian Ethical Committee (EudraCT Code Numbers 2017-004457-17 and 143AOR2017). Subsequently, an International Working Group (IWG) on Thalassemia was formed and it met in Palermo, Italy, on September 15th and 16th, 2017. Indicators of phenotype severity thought to be most pertinent in defining disease severity were shared among the IWG based on their expertise as well as on expert opinion reported on literature. These data were collected and stored on IHR platform (www.sanitasicilia.eu/IWG ). In order to define the prognostic score (PS) a retrospective multicenter case-control study was carried ahead. Overall, clinical findings of 7910 patients who attended the IWG centres from 1976 to 2018 were collected (Tab. 1). The study was based on 5657 cases that developed complications and 2253 controls that didn't develop any complications. The term "patient" was used both for cases and for controls. The variables used for the scoring system development were reported in Table 2. The PS was built using a Conditional Logistic Regression Model (CLRM) (DW. Hosmer, Jr., 2013). The full data-set was split into two data-set containing Group A and Group B patients. Group A included transfused TDT and NTDT patients, while Group B included only no transfused NTDT patients. This was necessary because of the variable "age at first transfusion" was absent in no transfused patients. The two PS will refer as Score A and Score B, respectively. The Stata 12 (StataCorp, College Station, TX, USA) was used for all analyses. Results Overall, the analysis was performed on 5657 cases (2812 Females, age at follow up 34.7±12.9) with a mortality of 8.5% and 2253 controls (1136 Females, age at follow up 22.1±12.8) with a mortality of 1.9%. Table 3 shows complications and deaths in the full data set. Moreover, it even suggests, as single patient may have more than one complication and that the cardiac complications followed by the cancer and infection were the most common. Table 4 shows the statistically significant variables for the calculation of the score. The age of the patient and at first diagnosis, the mean Hb, AST, ALT and the Left Ventricular Ejection Fraction (LVEF) were the statistically significant variables at CLRM analysis, for the Group A. The formula for the Score A=1.1x(Age)+0.9x(Age at first diagnosis)+1.3x(Hb mean)+1.006x(AST)+1.02x(ALT)+ 0.9x(EF). The age of the patient, the mean Hb and the LVEF were the statistically significant variables at CLRM analysis for the Group B. The formula for the Score B= 1.05x(Age)+1.001x(Hb mean) +0.9x(EF). Finally, Table 5 shows the application of these formulas to the full data set, defining five well-distinguished prognostic categories (Very low, Low, Intermediate, High, Very high). Conclusions Following appropriate validation, we propose that the severity scoring system described here could be developed into a practical tool for widespread clinical application, not only to evaluate patient status and classify disease subgroups, but also to inform treatment decisions and monitor patient progress in response to therapy. Finally, the use of this scoring system may help to select appropriate candidate for innovative treatment. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support. Vichinsky:bluebird bio: Consultancy, Research Funding; GBT: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding.

Introduction. A prospective magnetic resonance imaging (MRI) study demonstrated a good control of myocardial iron overload (MIO) in terms of prevention and treatment in children with thalassemia major (TM). The aim of the present study was to evaluate if changes in MIO were related to baseline hepatic iron or changes in hepatic iron overload (HIO). Methods. We considered 68 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) project with less than 18 years at the first MRI scan and who performed a follow-up (FU) study at 18±3 months. Myocardial and hepatic iron burdens were quantified by the T2* technique. The value of 20 ms was used as conservative normal value for the global T2* value. Liver T2* values were converted into liver iron concentration (LIC) values. A LIC Results. Thirty-six patients were females and mean age at the time of the baseline MRI was 13.74±3.09 years. Baseline global heart T2* values were 29.72±11.21 ms and 16 (23.5%) patients showed significant baseline MIO. The percentage changes in global heart T2* values per month in the whole patient population were 0.66±1.70 and they resulted significantly higher in the 16 patients with significant baseline MIO versus the patients with no baseline MIO (1.99±2.53% vs 0.25±1.09% ms; P=0.002). Percentage changes in global heart T2* values per month were not influenced by initial MRI LIC values (R=0.048; P=0.695) (Figure 1A) and were comparable among the 4 groups of patients identified on the basis of baseline MRI LIC values (14 no HIO: 0.29±1.12% vs 21 mild HIO: 0.75±1.56% vs 15 moderate HIO: 0.82±2.03% vs 18 severe HIO: 0.71±2.00%; P=0.876). Percentage changes in global heart T2* values per month were not associated to final MRI LIC values (R=-0.134; P=0.277) (Figure 1B). The correlation between % changes in global heart T2* and MRI LIC values did not reach the statistical significance (R=-0.244; P=0.067) (Figure 1C). In patients with baseline MIO no correlation was found between % changes in global heart T2* values per month and initial MRI LIC values (R=-0.325; P=0.219) or % changes in MRI LIC values per month (R=-0.353; P=0.180). Conclusion. In pediatric TM patients changes in cardiac iron are not correlated to baseline MRI LIC values and changes in hepatic iron. So, our data seem not supporting the hypothesis for which it is necessary to clean the liver before removing iron from the heart. Figure 1 Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures. In this setting, the determination of left ventricular ejection fraction (LVEF) offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF≥7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF≥7% had higher (84.76%) predictive value. Finally, Kaplan-Meier survival curves of thalassemia major patients with LVEF≥7% showed a statistically significant decreased probability of survival for heart disease (p=0.0022). However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial.

The prognosis of beta-Thalassemia major and other congenital hemoglobinopathies has profoundly changed over the last decades. Moreover, only few countries in Europe provide dedicated services and the description of the measures for patients monitoring and treatment is overall very scarce. The HTA-Thal project is aimed to identify the services available in Italy and to collect epidemiological and clinical data on the thalassemic population (HTA-Thal Registry).A map of the existing centers was created and two electronic questionnaires were completed with information on the services and patients.On 182 centers identified, 60 completed the two questionnaires. Centers resulted to be extremely heterogeneous in terms of size, age of patients in care, and services availability. The transition of pediatric patients to adult centers was not guaranteed. Thousand eight hundred and seventy-three beta-Thalassemia major patients (of which 259 pediatrics), regularly transfused, were registered. Deferasirox is the most used chelator as monotherapy (616 patients) and its use prevails in younger patients. A higher number of patients (847 patients) use Deferoxamine, either alone (448 patients) or in combination with DFP (399 patients), while 782 patients use Deferiprone alone (383 patients) or in combination (399 patients). 31.6 and 66.6% of centers were not equipped for specialized visits or local MRI, respectively. Centers with 30-80 patients show the high percentage of patients appropriately monitored when compared to smaller or bigger centers.This analysis confirms the importance of patients' registries for the collection of large datasets and the need for dedicated 'specialized centers' equipped to provide the best standard treatment to patients.

Introduction. Chronic iron overload may represent a serious complication of potentially lifesaving blood transfusions in different haematological diseases. Excess iron deposits in various tissues of the body, particularly the liver, heart, and endocrine organs (Cappellini. Thalassaemia International Federation, 2014). This process leads to tissue damage and ultimately to significant morbidity and mortality (Musallam. Haematologica 2013). Indeed, organ failure due to chronic iron overload may represent the major cause of death in patients with different haematological diseases who receive blood transfusions regularly without appropriate chelation therapy (Inati. Pediatr Blood Cancer 2011; N Engl J Med 2000; Cleve Clin J Med 2005). The main aim of this study was to look for the relationships between changes in LIC and changes in serum ferritin (SF) level, during real life experience with larger setting of patients with haematological diseases and different chelation regimens, previously described at baseline, according to the LICNET protocol (Vitrano et al., Eur J Haematol 2016). Methods. This was a cross-sectional study of patients with haematological disorders attending 9 Italian centres participating in the LICNET. The LICNET protocol was approved on December 4, 2012 by our Ethical Committee. The underlying diagnoses were regularly transfused Thalassemia Major (TM), Thalassemia Intermedia (TI), Sickle Cell Disease (SCD), Myelodysplastic Syndrome (MDS), Diamond-Blackfan Anemia (DBA). Transfused status was defined as receipt of ≥7 mL/kg/month of packed red blood cells. The inclusion criteria for the cross-sectional analysis were: 1) underlying diagnosis above described; 2) determination of two R2-MRI scans performed as part of the network, for those patients presenting between February 2013 and December 2016; 3) transfusion dependence; 4) same chelation treatment at T0 (MRI1) and T1 (MRI2) . The settled R2-MRI protocol at the Centre follows that of St Pierre et al. (St Pierre et al. Magn Reson Med 2014). Descriptive analysis was provided as means, standard deviations, medians or percentages. Three classes of risk (low, intermediate and high), on the basis of LIC values ( 15 mg Fe/g dw ) were considered to evaluate the control of iron body burden during the study period. LIC comparisons at MRI1 and MRI2 were made using t -test and/or Wilcoxon test. All p -values are two sided with the level of significance set at Results. A total of 130 patients were evaluated, with a median age of 35 years (range: 6-78). The median duration (range) between MRI1 and MRI2 days was 483 (184-1076). Patients' characteristics for the considered chelation regimens are summarized in Table 1. Overall patients, across all chelation regimens, showed a statistically significant difference in variation of LIC between MRI1 and MRI2 (p=0.011, Table 2). Overall variation of LIC, during a period of 483 (184-1076) days, was -0.8 (-29.0-33.0) mg Fe/g dw. Median changes in LIC (range), mg Fe/g dw for single chelation regimen are reported on Tab. 2. Changes in LIC determinations, during the period of the study, according to the baseline values, are shown on Fig. 1: Overall 7.7% of patients, across different chelation regimens and during a period of 483 (184-1076) days, moved from high risk group (LIC >15 mg Fe/g dw) to intermediate risk group (LIC 7-15 mg Fe/g dw) with stabilization of iron overloading in patients in low risk group at baseline; all chelation regimens were able to move LIC from high risk group to intermediate risk group. In the other combination group, the patients moved from the intermediate risk group to the low risk group. Median changes in SF level (range), ng/ml for overall patients and for single chelation regimen are reported on Tab. 2: Overall patients, across all chelation regimens, did not show any statistically significant difference in variation of SF between MRI1 and MRI2 (p= 0.566, Table 2). Conclusions. In conclusion, SF level trends are unable to predict changes in LIC, even in well chelated patients with haematological disorders. Therefore, variations of SF level must be interpreted with caution and confirmed, when it is possible, by direct measurement of LIC for more correct management of chelation treatment. Disclosures Oliva: Celgene: Consultancy; Amgen Inc.: Consultancy; La Jolla: Consultancy; Novartis: Consultancy; Janssen: Consultancy.

Introduction. Thalassemia Syndromes (TS) are currently categorized as transfusion dependent (TDT, primarily Thalassemia Major patients) and non transfusion dependent (NTDT, primarily Thalassemia Intermedia patients). TDT includes patients who need regular transfusions for survival with at least ≥7 ml/kg/month of packed red blood cells. NTDT is a term used to label patients who do not require lifelong regular transfusions for survival, although they may require occasional or even frequent transfusions in certain clinical settings and usually for defined periods of time. Therefore, the current TS classification suggests two defined classes of disease severity, TDT and NTDT, with different prognosis. However, recent survival studies in Western and Eastern countries showed that life expectancy of TDT is today quite similar to that of NTDT (Vitrano et al. Br J Haematol. 2017; Rajaeefard et al. Epidemiol Health 2015). The main aim of this study was to revisit the dichotomous classification of TS towards a classification including a "continuum" of the same disease divided in multiple stages according to the severity of phenotypes. Methods. This was a retrospective study on patients with TDT and NTDT, born after February 13, 1965 (data of approval of Deferoxamine chelation treatment), and attending 9 Italian centres. Our Ethical Committee approved the protocol on May 25, 2017. Focusing on clinical severity indicators, a cluster analysis was performed to explore if the current TS classification fits with two classes of risk, regardless if the patients had TDT or NTDT. The following indicators of clinical severity were selected: 1) age at first transfusion, years; 2) age at starting chelation, years; 3) transfusion therapy (yes/no); 4) Mean serum ferritin levels, ng/ml; 5) number of complications. Cluster analysis was applied at these indicators with the task of grouping a set of statistical units in such a way that units in the same group (cluster) will be more similar to each other than to those in other clusters. If current classification fits with clinical severity of TS, only two classes of risk matching TDT and NTDT should be identified. Results. Overall 1547 patients, 1332 with TDT (mean age 35.6±0.2 years) and 215 with NTDT(mean age 38.4±0.5years), were included in the study. Mean age at first transfusion was 1.5±0.04 years and 8.4±9.4 years in TDT and NTDT, respectively.Mean age at starting chelation was 4.6±0.1 years in TDT and 13.6±11.4 years in NTDT. Splenectomy was more common in NTDT (80.2%) than TDT ( 51.9%). Diabetes, heart failure and hypogonadism were most frequent in TDT, while cirrhosis was equally distributed. Figure 1 shows results from cluster analysis suggesting that it was not possible to classify TS only into two separate groups. The two obtained clusters intersect an area were patients with TDT and NTDT had very similar clinical features. Patients could not be divided by their clinical profiles between TDT or NTDT distinct groups (Fig. 1). Table 1 shows some TDT and NTDT patients allocated in two different clusters but with very similar clinical profiles. Conclusions. Cluster analysis suggests that the classes of risk of TDT and NTDT may not fit with current classification of TS. Indeed, some patients are detected in the same area of the clusters, independently from onset of diagnosis. This could be due to the presence of a "continuum" phenotype from NTDT to TDT. However, an effect of conventional treatment in improving phenotype of patients with TDT could be not excluded. Therefore, to validate this hypothesis, these data have to be confirmed in a larger population, encompassing different intensity of conventional treatment. In conclusion, although these results call for a potential revision of the clinical classification of thalassemia based on strict categories of severity towards a classification including a "continuum" of the same disease divided into one that manifests in categories (Classes of Risk), this hypothesis must be validated with larger setting of patients and discussed inside of International Working Group of expert opinion leaders on this field. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

Background— Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients. Methods and Results— We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy ( P P =0.001 and P P P =0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients. Conclusions— Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age.

The management of patients with non-transfusion-dependent thalassaemia (NTDT) has been a challenging task: in fact, within this conventional definition, clinicians have to deal with a great variety of syndromes mixed in terms of their molecular background, clinical course, and severity which share only the characteristics that are not entirely dependent on transfusions [1, 2]. In fact, NTDT phenotypes include patients with β-thalassemia intermedia, hemoglobin E/β-thalassemia, and Hemoglobin H disease (α-thalassemia intermedia) but also those with structural variant of hemoglobin associated with “α” or “β” thalassemia in heterozygous condition which often have analogous characteristics [3]. However, among different genetic entities of NTDT, the lack of a clear genotype-phenotype relationship further complicates this complex and extensive scenario in clinical practice [4]. Thus, despite the availability of recent guideline from Thalassemia International Federation, the strength of several treatments and follow-up recommended strategies should be confirmed in selected population [5]; in fact, most of these recommendations arise from retrospective and cross sectional studies where different patients were heterogeneously treated along their life with occasional transfusions, iron chelation, and splenectomy. Furthermore, in clinical practice, most of these recommendations are difficult to transfer into the “wide-spectrum” of phenotypes particularly in the case of patients first diagnosed in adult life. This special issue was launched to provide some insights into this wide subject, which is continually evolving. Out of the five articles published in this special issue on NTDT, two are updated reviews. It is well worth it to note that one focused on the role of oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) as a potential additive contributor to cell injury, tissue damage, and hypercoagulability observed in patients with NTDT; the other was devoted to expanding the emerging setting of endocrine and bone disease in NTDT. We collected also three original articles, two describing the profile of HbH disease in Taiwan and its incidence in Lebanon, respectively, and one evaluating again the endocrine and bone disease in β-thalassemia intermedia patients. Obviously, some of this epidemiological information could be only of regional interest but certainly adds some more clinical useful information. In conclusion, despite the great effort and benefit to encompass such a variety of syndromes in the acronyms NTDT, we should be always prepared to face the limitation of mixing heterogeneous patients within a single category. Further studies are needed to better define and compare at clinical and molecular level the different genetic entities of NTDT. The recent finding of similar degrees of anemia but diverse patterns of the GDF15-hepcidin-ferritin axis between β-thalassemia intermedia and HbH disease in a Sardinian series should stimulate extending such comparative evaluation among all different classes of NTDT [6]. We hope that readers of this special issue will find our articles accurate and updated and will focus on the need of developing more studies in this intricate and not fully explored setting. Paolo Ricchi Aldo Filosa Aurelio Maggio Suthat Fucharoen

The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value

Summary The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients’ age ranged from 4 2t o 97 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value

Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) technique is the only validated non-invasive approach used for detecting macroscopic myocardial fibrosis. Galectin-3 has been shown to participate in tissue fibrogenesis and was already associated with LGE-assessed myocardial replacement fibrosis in a cohort of patients with non-ischemic dilated cardiomyopathy (NICM). Our aim was to investigate the relationships between galectin-3 circulating level and myocardial fibrosis in patients with thalassemia major (TM) who underwent CMR technique during the Myocardial Iron Overload in Thalassemia (MIOT) project. All patients underwent also an extensive biohumoral characterization, including Troponin, NT Pro BnP, BNP, VES, PCR assay. At UOSD Malattie rare del globule Rosso of Cardarelli hospital (Naples, Italia), between January 2015 and March 2016, all patients who underwent contrast-enhanced CMR were progressively enrolled to test Galectin-3. Eighty-six patients were evaluated (males 43%; age 37, SD 8 years): six (7%) had diabetes mellitus (DM), 64 had anti-HCV antibodies and 28 (32%) were HCV RNA positive. Median galectin-3 value was 14.04ng/mL (5.26 ng/mL), and LGE was detected in 42 (49%) patients. Patients with LGE had higher galectin-3 than those without (14.48 ± 5.98, vs 13.63 ± 5.98), but without a statistically significant difference (p=0.109). Galectin-3 was significantly associated with age (R=0.34; p=0.001), but not with sex. Patients with DM, with anti-HCV antibodies and with HCV-RNA positivity, had significant higher level of Galectin 3 with respect to those without (22.5± 11.1 vs 13.4± 4, p=0.009; 14.9 ± 5.4 vs 11.5± 3.7, p=0.001; 16.2 ± 6.5 vs 13± 4.2, p=0.011, respectively). No correlation was found between Galectin 3 and other tested biochemical variables and iron overload and cardiac parameters. In conclusion, in our cohort of TM patients there was a great prevalence of myocardial fibrosis. In patients with myocardial fibrosis, the level of galectin-3 was higher and comparable to that found in a previous study performed in patients with NICM, but not significantly different with respect to those without fibrosis. The elevated prevalence of patients with previous exposure to HCV virus and/or DM and/or iron overload may significantly influence Galectin-3 level limiting the ability of the marker to identify patients without fibrosis. Disclosures De Franceschi: F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Funding. Pepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

Background and Aim: Direct-acting antiviral drugs (DAAs) have a very high efficacy in patients with hepatitis C virus (HCV) infection, but they have not been extensively used in patients with haemoglobinophaties. To evaluate the safety and efficacy of DAA regimens in this subset we used the ITHACA-SITE dataset, which includes patients with haemoglobinophaties and chronic HCV liver disease treated in Italy. Patients and methods: Between March 2015 and June 2016, 121 patients included in the ITHACA-SITE dataset started DAA regimens. Cirrhosis was defined by FibroScan®showing≥12 kPa performed within 6 months before the treatment. Regimen choice and use of ribavirin were based on viral genotype and stage of disease, according to guidelines. Negative HCV RNA at week 12 of post-treatment follow up was considered as Sustained Virological Response (SVR). Results: The mean age of 121 patients was 42 years, 75 (62%) were males, 101 (83.5%) had β-thalassemia major, 9(7.5%) had β-thalassemia intermedia and 10 (8.3%) had sickle cell disease. Sixty-six patients (54%) had the diagnosis of chronic hepatitis and 55 (46%) hadthe diagnosis of cirrhosis. The prevalence of HCV genotypes (G) was: G1a 6 (5%), G1b 70 (57.8%), G2 31 (25.6%), G3 6 (5%), G4 8 (6.6%). Fifty-six patients (46.3%) were Peg-interferon (P) and Ribavirin (R) naïve and 65 (53.7%) were P/R experienced, 20 patients (16.5%) had diabetes and 29 (24%) had heart disease. By June 2016 63 patients (52%) had concluded the treatment and 33 (27.3%) had concluded the post-treatment follow-up. By ITT, the rate of response at the end of treatment (ETR) was 100% (63/63) and 94% (31/33) of patients achieved a SVR. No patients stopped treatment because of adverse events. No interference with chelation therapy was observed. Conclusions: Use of DAAs regimens in practice is safe and effective in patients with haemoglobinophaties and cirrhosis or chronic hepatitis due to HCV. The therapy is indicated also in patients with co-morbidity. The lifetime utility of HCV eradication in terms of reduction of events and overall survival needs evaluation in long-term observational cohorts. Disclosures Piga: Novartis: Research Funding; Apopharma: Honoraria. Di Marco:Gilead: Research Funding. Forni:Novartis, Celgene: Research Funding.

Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2* Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

Background: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. Objectives: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. Methods: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 ± 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 ± 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 ± 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (DCO), corrected for both Hb values (DCO*) and alveolar volume (KCO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. Results: All patients in group A showed normal PFTs, DCO* and KCO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced DCO* (63 ± 8%), elevated KCO values (120 ± 14%), a variable degree of hypoxia (PO2 82 ± 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced DCO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, DCO* was negatively correlated with both serum ferritin (r = –0.58; p < 0.05) and age (r = –0.57; p < 0.05). Conclusions: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.

A retrospective study was performed to explore the effect of splenectomy on iron balance in thalassemia major (TM).Twenty two TM patients treated with splenectomy were compared with a control group (non-splenectomized patients) matched for sex, age, pretransfusional Hb, chelation therapy, and duration of follow-up in a retrospective study to evaluate blood consumption, iron intake, and serum ferritin during an overall observation period of 6 yrs before and 10 yrs after splenectomy.Splenectomy improved parameters of iron balance, determining a significant reduction in blood consumption (P 0.01), iron intake (P 0.01), and serum ferritin (P 0.01). Comparing the two groups, blood consumption and iron intake were similar in presplenectomy period (P 0.05), but serum ferritin was significantly higher in splenectomized patients (P 0.01). After splenectomy, blood consumption and iron intake were significantly lower (P 0.01) in splenectomized group while serum ferritin did not differ significantly (P 0.05) between two groups, except for the first year (P 0.05).Splenectomy determines immediate drop in blood consumption and iron intake but slow downtrend of ferritin; direct measurements of iron overload, such as magnetic resonance studies, are needed to better understand the effect of splenectomy on iron balance parameters. Tailoring chelation therapy and eventually its intensification seem more efficient measures to manage iron accumulation in TM and to lower iron level to safety threshold.

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 sixtyeight patients with thalassemia major followed for at least 5 years 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.

Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described. Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015. Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) . The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p- value Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one's. Moreover, the TM risk of death has been decreased from 6.8 to 2.8 (Cox Model HR 2.8 (1.7), p- value=0.099). These findings, if further confirmed, suggest as, in Western countries, our approach for genetic counselling of "at risk couples" for TM should be reconsidered. Table 1. Causes of death in Thalassemia Major and Thalassemia Intermedia patients. Diagnosis Causes of Death TM n (%) TI n (%) Cancer 3 (7,5) 5 (38,5) Heart Damage 16 (40,0) 2 (15,4) Infection 3 (7,5) 3 (23,1) Multi Organ Failure 1 (2,5) 0 (0,0) Stroke 1 (2,5) 0 (0,0) Liver Failure 3 (7,5) 1 (7,7) Not Available 11 (27,5) 1 (7,7) Other complications not related to Thalassemia 2 (5,0) 1 (7,7) Total 13 40 Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

Introduction: Recently, the ability of LIC (liver iron concentration) and serum ferritin in predicting myocardial iron overload (MIO) has been challenged by magnetic Resonance Imaging (MRI) monitoring which demonstrated no or weak correlation between serum ferritin or LIC and MIO. Anyway, the role of this traditional markers could result particularly useful in pediatric population, where MRI assessment is difficult to carry out, because of early age, scarce collaboration or limited availability. So, we derived objective thresholds for these markers for predicting cardiac T2* Methods: From the 2171 patients with hemoglobinopathies enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we retrospectively selected 107 paediatric patients with thalassemia major (TM) (61 boys, median age 14.4 years). MIO was assessed using a multislice multiecho T2* approach. Hepatic T2* values were assessed in a homogeneous tissue area and converted into LIC. Results: Twenty-three patients (21.5%) showed an abnormal global heart T2* value and none of them was under 7.9 years of age. Serum ferritin was negatively correlated with global heart T2* values (r=-0.425; P There was a significant negative correlation between global heart and MRI LIC values (P=-0.436; P Conclusion: A weak connection between serum ferritin levels or hepatic iron and cardiac iron was demonstrated in our pediatric population. Anyway, MRI LIC≥14 mg/g/dw and serum ferritin levels≥2000 ng/ml were found to be significant risk factors for a global heart T2* value Figure 1. Figure 1. Disclosures Pepe: Novartis: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Chiesi: Speakers Bureau.

Introduction. This was a cross-sectional study of patients with hemoglobinopathies attending 13 Italian centers participating in the LICNET (Liver Iron Cutino Network) network promoted from Piera Cutino partnership and instituted by our center (Campus of Haematology Franco e Piera Cutino-A.O.O.R. Villa Sofia Cervello, Italy) on February 2013. LICNET is addressed to the diagnostics of iron overload in liver by R2 MRI (Ferriscan®) in patients with hemoglobinopathies. Ferriscan is a rapid scan method now available (10 minutes). This tool is crucial to have accurate and reliable measures for iron body burden control in hemoglobinopathies. Methods. Data included patients with β-thalassemia major (TM) (regularly transfused) (TX), β-thalassemia intermedia (TI) (both TX and non-transfused) (non-TX), and sickle cell disease (SCD) (both TX and non-TX). The main aim of the study was to evaluate how serum ferritin levels (SFLs) predict liver iron concentration (LIC) in different hemoglobinopathies, and to have valuable information about prognosis and response to therapy. In particular, to identify SFLs that best predict LIC thresholds of clinical significance (7 and 15 mg Fe/g dw) by identifying levels with highest sum of sensitivity and specificity was used the receiver operating characteristic (ROC) curve analysis. Results. A total of 363 patients were evaluated in this analysis, with a mean age of 35.6 ± 13.0 years (range: 6-76) and including 160 (44.1%) males. The underlying diagnosis were β-TM (n=204, 56.2), β-TI (n=102, 28.1%), and SCD (n=57, 15.7%). Among β-TI patients, 60 (58.8%) were on transfusion therapy. Similarly, in patients with SCD 34 (59.6%) were on transfusion therapy. The mean LIC in the study population was 7.8 ± 9.6 mg Fe/g dw and the median was 4.0 mg Fe/g dw. Across underlying diseases, LIC distribution was as follows: β-TM (mean: 9.0 ± 10.7, median: 4.9 mg Fe/g dw), TX β-TI (mean: 7.1 ± 7.3, median: 5.0 mg Fe/g dw), non-TX β-TI (mean: 5.1 ± 6.0, median: 3.2 mg Fe/g dw), TX SCD (mean: 8.5 ± 11.0, median: 4.5 mg Fe/g dw), and non-TX SCD (mean: 3.1 ± 1.9, median: 2.4 mg Fe/ g dw). It was apparent that TX patients irrespective of underlying diagnosis have a comparable proportion of patients with high LIC risk categories (>7 mg Fe/g dw) (p=0.627). Among chelated patients, LIC distribution was as follows: Deferoxamine (DFO) (mean: 7.3 ± 8.5, median: 4.7 mg Fe/g dw), Deferiprone (DFP) (mean: 11.6 ± 11.4, median: 8.4 mg Fe/g dw), Deferasirox (DFX) (mean: 7.8 ± 10.3, median: 3.2 mg Fe/g dw), DFO+DFP (mean: 8.2 ± 10.6, median: 4.5 mg/ Fe g dw), and other combinations (mean: 6.5 ± 4.0, median: 5.1 mg Fe/ g dw), with a statistically significant difference noted between groups (p =0.009) with the highest median among chelated patients noted in DFP treated patients and lowest median noted in DFX treated patients. For underlying disease groups, ROC curve analysis showed that SFLs that best predict LIC thresholds of 7 and 15 mg Fe/g dw varied, although patients with β-TI showed lowest SFLs to predict these thresholds especially non-TX patients (Fig. 1, Fig.2). Discussion. This study suggest as high values of LIC are present even in patients with TI or SCD, confirming that gastro-intestinal iron absorption is one of the main mechanism for secondary iron overloading. Moreover, close to 20% of patients with non-TX β-TI continue to have high LIC thresholds, while none of non-TX patients with SCD have LIC values > 7 mg Fe/g dw. The evidence that SFLs of 900 ng/mL are related in β-TI with LIC > 15 mg Fe/g dw (Fig. 2) suggests as chelation treatment could be reconsidered earlier in this cohort of patients. Finally, these findings suggest as LIC is predicted by different SFLs according to the different types of hemoglobinopathy. Figure 1. Receiver operating characteristic curve analysis of serum ferritin level for predicting LIC>7 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 1. Receiver operating characteristic curve analysis of serum ferritin level for predicting LIC>7 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 2. Receiver operating characteristic curve analysis of serum ferritin levels for predicting LIC>15 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 2. Receiver operating characteristic curve analysis of serum ferritin levels for predicting LIC>15 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Disclosures No relevant conflicts of interest to declare.

Sexual maturation and growth during induction of puberty with oral ethinylestradiol at low doses were evaluated in seven thalassemic girls, aged 13.6–16.5 years with hypogonadotropic hypogonadism (group 1). They were compared with nine thalassemic girls, aged 9–11.4 years with spontaneous puberty (group 2). Estrogen therapy was started at chronological age (CA) of 14.3 ± 1.12 (M ± SD) years corresponding to bone age (B A) of 11.4 ± 1.07 years. Five patients had vaginal bleeding after about 1 year of therapy, attaining a Tanner pubertal stage of B3–B4. Two patients lacking vaginal bleeding after 15 months of continuative therapy, received estrogen with the addition of medroxyprogesterone acetate. Vaginal bleeding occurred at CA of 15.7 ± 1.0 year (BA 13.1 ± 1.01 years). In group 2, at onset of puberty CA was 10.3 ± 1.05 years (BA 10.1 ± 1.05 years) and at menarche CA was 12.6 ± 0.46 years (BA 12.4 ± 0.32 years). After 3 months of therapy, all patients of group 1 showed a height velocity peak of 7 ± 1.9 cm smaller than in group 2 (cm 9.1 ± 0.98). Height gain until vaginal bleeding, in group 1 (4.8 ± 1.57 cm) was smaller than in group 2 (11.9 ± 3.66 cm). There was no significant difference in either mean height at first vaginal bleeding or in predictive final height between the two groups. No side effects were observed during therapy. It is interesting to note that patients of group 1 showed a serious degree of osteoporosis; in fact, the mean value of bone mineral density was smaller than in Italian normal girls (0.49 ± 0.08 vs. 0.61 ± 0.06 (g/cm2), p

In β-thalassemia major (β-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 versus L1 alone iron chelation therapy in β-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 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statistically, a decrease of serum ferritin levels 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 β-TM patients who may not be able to receive other forms of chelation treatment.

5165 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac and liver iron in TM patients treated with sequential deferiprone–deferoxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFP-DFO vs DFX in a cohort of TM patients by quantitative MR. Methods: Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFO versus the 44 patients treated with DFX between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Results: The doses of the sequential treatment were DFP 70±14 mg/kg/d for 4 d/w and DFO 42±8 mg/kg/d for 3 d/w, the dose of DFX was 26±6 mg/kg/d. Excellent/good levels of compliance were similar in the 2 groups (DFP-DFO 96% vs DFX 100%; P = 0.36). At baseline the 2 groups were homogeneous for cardiac and liver iron. Among the patients with no significant myocardial iron overload at baseline (global heart T2* 3 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95% vs DFX 96%; P = 1.0). Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms), only in the DFX group there was a significant improvement in the global heart T2* value (11 ± 5 ms at baseline versus 16 ± 8 at 18 ± 3 months, P = 0.0001) and in the number of segment with a normal T2* value ( P = 0.003). The improvement in the global heart T2* was not significantly difference in the DFP-DFO versus the DFX group (mean difference global heart T2* 2.2 ± 4.1 ms versus 4.6 ± 4.8 P = 0.2). The changes in the mean serum ferritin level were not significantly different between groups. In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant between groups (mean difference liver T2* 0.9 ± 2.1 ms vs 2.4 ± 5.2; P = 0.3). Conclusions: Prospectively in the clinical setting over 15 months we did not find significant differences on cardiac and liver iron by quantitative MRI in TM patients treated with sequential DFP–DFO versus the TM patients treated with DFX. Disclosures: No relevant conflicts of interest to declare.

Abstract 2157 Introduction: Magnetic Resonance Imaging (MRI) by the T2* technique allows highly reproducible and non invasive quantifications of myocardial iron burden and it is the gold standard for quantifying biventricular function parameters. It is important to determine the appropriate age to start MRI screening, because its high cost. Few data are available in the literature and they are contrasting. So the aim of this study was to address this issue in our paediatric patients with thalassemia major (TM). Methods: We studied retrospectively 72 patients (47 males, 4.2–17.9 years old, mean age 13.03 ± 3.70 years), enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network. Myocardial iron overload was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: The global heart T2* value was 29.7 ± 11.2 ms (range 6.2 – 48.0 ms). No significant correlation was found between global heart T2* value and age (see figure). The global heart T2* value did not show significant differences according to the sex (male 30.2 ± 11.0 ms versus female 28.7 ± 11.8 ms, P=0.568). Sixteen patients (22%) showed an abnormal global heart T2* value ( Conclusion: The MRI screening for both cardiac iron overload and function assessment can be started for TM patients at the age of 7 years. At this age not sedation is generally needed. If the availability of cardiac MRI is low, the serum ferritin levels could be used as a discriminating factor. Disclosures: No relevant conflicts of interest to declare.