Cardiac MRI T2 Research Articles

N-terminal-pro-b-type natriuretic peptide levels and cardiac hemosiderosis in adolescent β-thalassemia major patients.

Background:Iron-induced cardiomyopathy remains the leading cause of mortality in patients with β-thalassemia major. Iron overload cardiomyopathy, which may be reversible through iron chelation, is characterized by early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of diastolic dysfunction.Aim:The aim of the study is to evaluate the diagnostic value of NT-proBNP as a surrogate marker of iron overload examined with magnetic resonance imaging T2-star (MRI T2*).Methods:Sixty-eight β-thalassemia major patients (10–18 years) with no signs of heart failure underwent NT-proBNP measurement before routine transfusion. All participants prospectively underwent cardiac MRI T2* examination within 3 months (median 19 days). Patients were divided as cardiac hemosiderosis (cardiac MRI T2* <20 ms) and nonhemosiderosis (cardiac MRI T2* >20 ms).Results:Of 68 patients, the male-to-female ratio was 1:1.1 and the median age was 14.1 years (range: 10–17.8 years). NT-proBNP levels were not different between hemosiderosis and nonhemosiderosis patients (P = 0.233). Further receiver operating characteristic analysis resulted in no significant correlation of NT-proBNP and MRI T2* (area under the curve 0.393, P = 0.233).Conclusion:Measurement of NT-proBNP levels cannot be used for early detection of cardiac iron overload in adolescent with β-thalassemia major.

Cardiac MRI T2* in Liver Transplant Candidates: Application and Performance of a Novel Imaging Technique to Identify Patients at Risk for Poor Posttransplant Cardiac Outcomes.

BackgroundIn end-stage liver disease, alterations in iron metabolism can lead to iron overload and development of iron overload cardiomyopathy. In liver transplant candidates, evaluation for cardiac iron overload and dysfunction can help to identify candidates at increased risk for peritransplant morbidity and mortality, though recommendations for pretransplant evaluation of cardiac iron overload are not standardized. Cardiac Magnetic Resonance Imaging T2* (CMRI-T2*) is a validated method to quantify cardiac iron deposition, with normal T2* value of 20 ms or greater. In this study, we sought to identify the incidence and predictors of iron overload by CMRI-T2* and to evaluate the impact of cardiac and iron overload on morbidity and mortality after liver transplantation.MethodsIn this retrospective single-center cohort study, all liver transplant candidates who underwent a pretransplant CMRI-T2* between January 1, 2008, and June 30, 2016, were included to analyze the association between clinical characteristics and low T2* using logistic regression.ResultsOne hundred seventy-nine liver transplant candidates who received CMRI-T2* were included. Median age was 57 years, 73.2% were male, and 47.6% were white. 49.7% had hepatitis C and 2.8% had hemochromatosis. Median Model for End-Stage Liver Disease score was 25. 65.2% were Child-Pugh C. In multivariable logistic regression, T2* less than 20 ms (n = 35) was associated with Model for End-Stage Liver Disease score of 25 or greater (odds ratio [OR], 3.65; P = 0.007), Child-Pugh C (OR, 3.42; P = 0.03), and echocardiographic systolic ejection fraction less than 65% (OR, 2.24; P = 0.01). Posttransplant heart failure occurred exclusively in recipients with T2* less than 15 ms. Survival was worse in T2* 10 to 14.9 versus T2* of 20 ms or greater (hazard ratio, 3.85; P = 0.003), but not for 15 to 19.9 versus T2* of 20 ms or greater.ConclusionsSeverity of liver disease and systolic dysfunction is associated with T2* less than 20 ms, though there was no difference in posttransplant outcomes between T2* 15 to 19.9 and T2* 20 ms or greater, suggesting that individuals with T2* of 15 ms or greater may be suitable transplant candidates. CMRI-T2* is an additional diagnostic tool in evaluating transplant candidates at high risk for posttransplant cardiac complications.

Cardiac Iron Overload: Correlation between MRI T2* &amp; Two Dimensional Strain Echocardiography in Children with b-Thalassemia Major

AbstractBackground: b-thalassemia is a group of inherited blood disorders that causes iron overload in the heart. Development of overt heart failure is delayed till the second decade of life. Early detection of cardiac iron overload is necessary before development of heart failure.Aim of the Study: Was to evaluate cardiac function in children with b-thalassemia major having iron overload and to Compare MRI T2* and doppler echocardiography in dem-onstration of iron deposition in cardiac muscles in those patients.Patients and Methods: Fifty children with thalassemia major were subjected to history taking, clinical assessment, laboratory assessment, Doppler echocardiography and MRI for cardiac iron load assessment.Results: There is a negative correlation between cardiac MRI T2* with age, ferritin and serum iron level. As regard correltion between MRI and doppler echocardiography there is a positive correlation between MRI T2* and diastolic echocardiographic parameters Tei index in patients with thalassemia Major.Conclusion: There is a significant correlation between MRI T2* and Doppler echocardiography in patients with b thalassemia major.

Phlebotomy for Pediatric and Young Adult Oncology Patients Treats Transfusional Iron Overload

Introduction:Pediatric and young adult oncology patients treated with intense chemotherapy and stem cell transplant regimens have a high incidence of transfusional iron overload.(Acquazzino and Schloemer et al, ASH 2015). Iron deposition can lead to significant complications including heart failure, arrhythmias, liver abnormalities, endocrine dysfunction and ineffective erythropoiesis, as well as increased cancer and mortality risk. However there is a paucity of data regarding recommendations for management of transfusionial iron overload in childhood cancer survivors. Consequently, long-term complications of transfusional iron overload specific to pediatric cancer survivors have not been assessed. We have instituted screening and phlebotomy based treatment algorithms for pediatric and young adult oncology patients with transfusional iron overload.Methods:We conducted a retrospective chart review of pediatric and young adults who after having completed oncology management, were diagnosed with transfusional iron overload through a screening algorithm, and then initiated phlebotomy treatment. Tiered screening occurred in patients who received at least 5 packed red blood cell (pRBC) transfusions. Patients were recommended for further evaluation and discussion of possible phlebotomy treatment if they had: (1) liver iron concentration (LIC) greater than 5 mg of iron/gram dry weight liver tissue as measured by ferriscan and/or (2) cardiac MRI T2* < 20 ms. Management of phlebotomy treatment was conducted according to Table 1. During phlebotomy patient iron status was assessed at least quarterly and phlebotomy discontinued with achievement of LIC <5 or normalization of ferritin and followed by imaging LIC assessment verification. Inclusion criteria: (1) diagnosis of childhood malignancy, (2) completed active cancer therapy, (3) received phlebotomy treatment for transfusional iron overload. Exclusion criteria included: Patients with known hereditary hemochromatosis and patients who received photopheresis. Descriptive statistics were employed to report the characteristics of the study population. Spearman correlations were utilized to describe the association between number of transfusions, LIC, ferritin, iron saturation and number of phlebotomy sessions. This study was approved by the Children's Hospital of Wisconsin Institutional Review Board prior to data collection.Results:Patient Demographics: We identified 25 pediatric and young adult childhood cancer survivors who underwent phlebotomy for transfusional iron overload. The mean age was 11.6 years (SD 6.1) and 10 (40%) were female. Oncologic diagnoses included ALL (36%), AML (8%), NHL (12%), Ewing sarcoma (16%), Osteosarcoma (4%), Neuroblastoma (12%) and CNS malignancies (12%).Transfusions/Phlebotomy/Diagnostic Tests: (Table 2) Patients received a median of 25.0 (IQR 17 - 34) pRBC transfusions. No patient had fewer than 10 transfusions. Median number of phlebotomy sessions was 6 (IQR 4-8) occurring over a median period of 0.36 years (IQR 0.28 - 0.59). Prior to phlebotomy, the median LIC was 7.5 mg/g (IQR 5.6-9.0) and median ferritin was 1110.0 ng/mL (IQR 700 - 2030). No patients demonstrated cardiac transfusional iron overload on T2* MRI (n=18). 23 (92%) patients have completed phlebotomy. One patient discontinued phlebotomy due to inability to safely obtain vascular access and no patients developed iron deficiency anemia. LIC was reduced by a median of 2.4 mg/g (IQR 1.1 - 3.6) and ferritin was reduced by median of 586 ng/mL (IQR 366-875). Correlation between number of transfusions received and phlebotomy sessions administered was poor (R2=0.017).Conclusions:Management guidelines are absent for transfusional iron overload in pediatric and young adult survivors of cancer. We demonstrate a phlebotomy algorithm that is an effective and well tolerated treatment for pediatric and young adult oncology patients with therapy related transfusional iron overload. Correlation between number of transfusions received and phlebotomy treatments required to remove deposited iron was poor necessitating serial assessments of iron status. Using this management algorithm, prospective studies can evaluate the effect of excess iron removal on iron overload complications in pediatric and young adult cancer survivors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with β-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 µg/L; cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2] ≥5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 ± 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 µg/L at baseline to 845.3 µg/L following 52 weeks of therapy (P < .001); 9 patients (33.3%) achieved a level of <500 µg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P < .001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P = .520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile.

Observation on the clinical effectiveness of deferasirox, deferiprone and desferrioxamine in the treatment of iron load in patients with thalassemia major

Objective To explore the clinical effectiveness of deferasirox, deferiprone and desferrioxamine in the treatment of iron overload in patients with thalassemia major. Methods Among the severe thalassemia patients with iron overload being diagnosis, treated and followed up in Guigang City People′s Hospital, fifty cases were tested by MRI T2 and were detected with cardiac and liver iron overload, the patients were selected and randomly divided into the deferoxamine treatment (DFO) group(18 case), deferiprone treatment (DFP) group (22 cases) and deferasirox treatment (DFX) group (10 case), The baseline data of the three groups were statistically analyzed.the serum ferritin (SF) value, the cardiac MRI T2 value and the liver MRI T2 value before and after treatment were measured. Results The patients completed the treatment, after 1 years of treatment, the serum SF value, cardiac and liver MRI T2 values of the patients were improved than those before the treatment (P 0.05); the differences in liver MRI T2 value among the three groups were not statistically significant(F=0.131, P>0.05), There were significant differences in heart iron load MRI T2 values among the three groups ((34.27 ± 6.30) ms vs.(23 ± 2.79) ms vs.(21.8 ± 2.20)ms, F=39.54, P<0.05). Conclusion Deferoxamine, deferiprone and deferasirox can effectively alleviate the iron load in patients with thalassemia major.in terms of cardiac iron overload, the curative effects of deferiprone treatment in patients with thalassemia is superior than desferrioxamine and deferasirox treatment, it is worthy of clinical promotion. Key words: Thalassemia Major; Iron Chelator; Serum Ferritin; MRI T2*Ttechnology

A Comparison Between MRIT2 and NT-ProBNP in Early Detection of Heart Diseases in Thalassemia Major Patients: A Cross-Sectional Study.

One of the most common causes of mortality in major thalassemia is cardiac complications. Despite existence of several methods for diagnosis of cardiac complications in thalassemia, this sequel persists as a major problem in these patients. The aim of this study is to compare the level of serum NT-ProBNP and cardiac MRI T2* in early detection and treatment of cardiac disorders in beta thalassemia major patients. 35 major thalassemic patients on regular transfusion were selected in our center from 2013 to 2014. All of the patients were at least 8years old. NT-ProBNP and MRIT2* analyses were carried out for these patients, and consequently the findings were compared together and analyzed. There is a strong correlation between NT-ProBNP and MRIT2* (p value<0.001) in early detection of cardiac disorders. NT-ProBNP is an important marker for diagnosis of cardiac complications before emergence of heart failure in thalassemic patients. Given the findings of this study, it is recommended that this marker be used on a regular basis for thalassemic patients on regular transfusion.

Soluble hemojuvelin in transfused and untransfused thalassaemic subjects.

The hemojuvelin-bone morphogenetic protein axis is the principal iron-dependent mechanism of hepcidin regulation. The determination of soluble hemojuvelin (sHJV) levels could allow for a better understanding of the pathophysiological mechanisms of hepcidin regulation in thalassaemia. We have assessed sHJV in 45 transfused and 15 untransfused thalassaemic patients in comparison with 15 healthy subjects, evaluating its relationships with some parameters of iron overload, anaemia and erythropoiesis. Untransfused thalassaemic patients had more severe anaemia and erythropoietic activity, while in transfused patients, the transfused RBCs reduced % reticulocytes and sTfR, increased serum indices of iron overload and iron stores in the liver (low MRI T2* values). sHJV levels were higher in patients than in controls and in untransfused in comparison with transfused patients. In the transfused group, we also found that sHJV values are significantly related to serum ferritin, cardiac MRI T2* and growth differentiation factor 15 and are sensitive to hepatitis C virus infection. These results suggest that sHJV synthesis seems to be affected by an erythropoietic/hypoxic signal in untransfused patients that have severe anaemia, while in regularly transfused subjects, it is influenced by iron stores.

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease.

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron-induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long-term (over the 5years prior to enrolment) mean serum ferritin (MSF), spot-ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty-two SCD patients (median age 15years) with transfusional iron overload were recruited from two U.S. institutions. Long-term MSF and spot-ferritin values significantly correlated with LIC by MRI-R2* (r=0·77, P<0·001; r=0·82, P<0·001, respectively). LIC by MRI-R2* had strong positive correlation with LIC by liver biopsy (r=0·98, P<0·001) but modest inverse correlation with cardiac MRI-T2* (r=-0·41, P=0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression.

Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis

Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown...

Interim Results from a Phase 2, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major

▪Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited.Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* <20 ms or liver iron concentration (LIC, by MRI R2) of ≥5 mg/g. The study included male and female TM patients ≥2 to <18 years old who had undergone HSCT with a washout period from immunosuppressive therapy of at least 3 months. Patients received DFX at an initial dose of 10 mg/kg/day with up titration every 3 months by 5 mg/kg/day per investigator judgment to a maximum of 20 mg/kg/day. Therapy continued for 52 weeks or until SF reached below 500 μg/L. Aside from AE monitoring, assessments were undertaken at baseline and every 28 days (unless closer assessments were need for dose initiation and adjustment) and included complete blood counts, biochemistry and urinalysis, and SF. MRI assessment of liver (R2) and cardiac (T2*) iron were also conducted at baseline and 52 weeks.Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p<0.001 (Figure 2). At week 52, 6 (33.3%) patients had reached SF <500 μg/L. LIC also significantly decreased from a median of 9.9 mg/g (range: 4.8-43) to 4.1 mg/g (range 0.9-8.5), p<0.001. Cardiac T2* increased from a median of 26.1 ms (range: 18.7-41) to 28.8 ms (18.5-44), p=0.605.Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. [Display omitted] [Display omitted] [Display omitted] DisclosuresDag:Novartis: Employment. Birkent:Novartis: Employment.

CHEST PAIN IN PATIENTS UNDER AGE 40: ARE WE GETTING IT RIGHT?

Chest pain in young patients may be a diagnostic challenge. “Non-coronary” etiologies are often considered. Criteria for pericarditis include chest pain, EKG changes, pericardial effusion and a friction rub. These findings can be absent or transient. Cardiac MRI(CMR) T2 STIR and late gadolinium

Fast, whole-heart, free-breathing 3D T2 mapping at 3T with application to myocardial edema imaging

Background Cardiac MRI (CMR) T2 mapping is a proven method for myocardial edema detection. However, the current approach requires multiple breath-holds and can take nearly 10-15 minutes to complete. Faster acquisitions could potentially improve patient comfort and costeffectiveness of CMR exams. the objecttive of this study is to develop and test a free-breathing, three-dimensional, cardiac MR approach which can yield fast, accurate, T2 maps of the whole left ventricle at 3T.

Role of Vitamin C As an Adjuvant Therapy with Different Iron Chelators in Young β-Thalassemia Major Patients: Safety and Efficacy in Relation to Tissue Iron Overload

▪Background: Treatment with antioxidants may neutralize the deleterious effects of oxidative damage by reactive oxygen species generated from labile plasma iron. Vitamin C has been known to increase the efficacy of desforaxamine (DFO). Few studies examined the influence of vitamin C supplementation in iron overloaded β-thalassemia major (β-TM) patients with oral chelators.Aim: To determine the beneficial effects of Vitamin C as an adjuvant to iron chelators in children and adolescents with β-TM and its relation to tissue iron overload.Methods: A randomized prospective study registered on ClinicalTrials.gov (NCT02083575) included 100 patients with β-TM recruited from the regular attendees of Thalassemia center. Inclusion criteria were β-TM patients 2-18 years with serum ferritin (SF) >1000-2500 ng/ml on regular transfusion-chelation therapy receiving the standard doses of Desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) in a ratio1:1:1. All the enrolled patients had vitamin C deficiency. Exclusion criteria included patients suffered from insulin-dependent diabetes, clinical cardiac and/or advanced liver disease. The thalassemia patients received vitamin C in a dose of 100 mg daily. Patients were followed-up for 6 months with assessment of transfusion frequency and index, complete blood count, vitamin C levels, serum iron, total iron binding capacity (TIBC), SF and transferrin saturation (Tsat), liver iron content (LIC) and cardiac magnetic resonance imaging T2* before and after therapy were assessed.Results: Laboratory variables at baseline were similarly distributed among patients receiving different iron chelating agents. Upon comparing baseline and post-therapy clinical and laboratory variables among the studied β-thalassemia patients; transfusion index was significantly decreased after 6 months of vitamin C therapy (p=0.03) and the number of transfused patients <3 weeks dropped from 66% to 57% although the difference did not reach a significant level. Hemoglobin level improved (p<0.01). SF, Tsat and LIC were significantly lower after treatment than baseline levels (p=0.048, p<0.01 and p=0.035, respectively). Cardiac MRI T2* and vitamin C levels increased 6 months after treatment (p=0.025 and p<0.001, respectively). Vitamin C supplementation to patients receiving DFO had significantly lowest transfusion index (p=0.035) with significant improvement in hemoglobin level and cardiac MRI T2* as well as decreased SF, Tsat and LIC (p<0.01). Patients on DFP or DFX showed non-significant improvement in hematological and radiological variables. Vitamin C level was negatively correlated to transfusion index, SF and LIC (p<0.01). Neither serious adverse reactions related to the chelators nor to Vitamin C administration have been reported.Conclusions: Vitamin C in a dose of 100 mg, as an adjuvant therapeutic agent increased the efficacy of DFO in reducing iron burden in the moderately iron overloaded B-TM with vitamin C deficiency; it showed marginal improvement with DFP and DFX. Higher doses of vitamin C therapy might be tried with evaluation of possible additional adverse events. DisclosuresNo relevant conflicts of interest to declare.

Liver and heart iron deposition status in patients with β thalassemia major: a multicenter study

To observe the status of iron deposition in patient with β thalassemia major, and to formulate appropriate treatment strategies. The data of status of transfusion and chelation in 135 patients aged from 6 years and 4 months to 17 years and 11 months with β thalassemia major were collected and analyzed. Serum ferritin levels were determined and cardiac and hepatic iron deposition was determined using MRI T2(*) technology. Of the 135 cases studied, 66 were male, and 69 were female, their average age was 12.1 years. Serum ferritin (SF) was determined for 111 cases, it varied from 1 086.8 µg/L to 15 011.5 µg/L. Among them, 16 cases had SF level <2 000 µg/L (14.5%) , in 41 cases SF were between 2 000 and 4 000 µg/L (36.0%) ;in 54 cases SF >4 000 µg/L (48.7%) . Liver MRI T2(*) results showed that in only 8 cases (5.9%) iron content in the liver was in normal range, 19 cases (14.9%) showed mild liver iron deposition;34 (25.2%) moderate and 74 (54.8%, the youngest one was only 6 years and 4 months of age) had severe iron deposition respectively. Cardiac MRI T2(*) showed that in 89 cases (65.9%) iron content in the heart was in normal range;19 cases (14.1%) had mild cardiac iron deposition and 27 (20.0%) presented severe iron deposition (the youngest one was only 9 years and 3 months of age) . SF level was obviously related to liver and cardiac iron deposition (MRI T2(*)) r and P value were -0.284, 0.003 and -0.374, 0.000 respectively. In 108 cases regular transfusion and chelation were delayed due to financial problem. The late and insufficient dosage administered and irregular chelation caused the higher SF level and the severe iron deposition. The survival status of β thalassemia major in China is worrisome. Majority of them had not received regular transfusion and chelation. Liver and cardiac iron deposition occur early and had a high incidence.

Efficacy and Safety of Deferasirox in β-Thalassemia Major Patients in Iran: A Prospective Study from a Single referral Center in Iran

Introduction: Herein, the results of a prospective study evaluating the efficacy and safety of treatment with deferasirox are studied in iron-overloaded patients with β-thalassemia major during an 18-month trial. Methods: Thirty patients who were previously chelated with deferoxamine with/without deferiprone, and fulfilled the inclusion criteria were recruited. Patients received an initial dose of 10–30 mg/kg/day. Liver and cardiac MRI T2* were evaluated before and after the trial. In addition, serum ferritin level was assessed every 3 months. Primary endpoint was regarded as significant improvement in the severity of liver and cardiac iron overload in severe and moderate cases, in addition to improvement or maintenance of the grade of severity in patients with mild iron overload or normal iron accumulation. Therapy was considered effective if primary endpoint was met in >50%. Results: Liver MRI values improved significantly (P = .002), achieving a 73.33% success rate. A successful outcome regarding myocardial iron overload was observed in 80%. Finally, an overall of 66.66% of patients met the success criteria. Secondary endpoint, regarded as safety and tolerability was reached by 93.33%. The most common adverse events were skin rash and gastrointestinal disturbance. A dose between 30 and 40 mg/kg/day, tailored to each patient was considered the optimal dose. Conclusion: Deferasirox proved as an efficient and safe chelating agent in our patients, specifically in mild to moderate iron overloaded patients.

Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload.

Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload.

Comparison Of Two Combination Iron Chelation Regimens, Deferiprone and Deferasirox Versus Deferiprone and Deferoxamine, In Pediatric Patients With β-Thalassemia Major

BackgroundPatients with severe iron overload may require a more rapid and efficient therapy for reduction in iron burden than what can be provided with chelation monotherapy. Combined chelation using deferoxamine (DFO) and deferiprone (DFP) is widely used to treat such patients, but the inconvenience of parenteral administration of DFO reduces the effectiveness of this regimen in many patients. Minimal data are available on the safety and efficacy of combined two orally active chelator agents. AimTo compare the safety, efficacy, compliance, treatment satisfaction, and quality of life (QoL) associated with two combination chelation regimens: DFP and DFO versus DFP and deferasirox (DFX). MethodsThis was a randomized, open-label trial registered as (NCT01511848) conducted at 2 treatment centers in patients aged 10 to 18 years with β-thalassemia major and severe iron overload (serum ferritin > 2500 μg/ L on chelation monotherapy, with 50% uptrend over the last 12 months). Patients were randomly allocated to one of two 12-month treatment regimens. All patients received DFP at a dose of 75 mg/kg/day, divided into 2 doses taken orally at 8 am and 3 pm. Those in Arm 1 additionally received DFO at a dose of 40 mg/kg/d delivered via subcutaneous infusion pump, starting at 10 pm, while those in Arm 2 additionally received a dose of DFX 20 mg/kg/d, taken orally at 10 pm. The primary efficacy endpoints were the difference between treatment groups in the change from baseline to 12 months of serum ferritin (SF) levels, liver iron concentration (LIC), and cardiac MRI. Secondary efficacy endpoints were the change from baseline to 12 months in QoL, using the Medical Outcomes Study Short Form health survey (SF-36). Serum ferritin was measured every 3 months, and liver and cardiac MRI T2* assessments were conducted every 6 months. Changes in all 3 measures were compared using 2-way ANOVA for repeated measures. The safety endpoint was the occurrence of serious adverse events during the study period. In addition, patients had complete blood count every 2 weeks, and monthly detailed clinical examinations that included blood sampling for serum creatinine, albumin/creatinine ratio, and liver function tests. Audiometric and ophthalmological assessments were conducted at baseline and 12 months. Assessments of compliance and of patient-reported outcomes (PROs) were assessed at weeks 424 and at end of study. ResultsA total of 96 patients were randomized. The arms were comparable with respect to baseline demographics, with a mean age of 14.9±1.8 years in Arm 1 and 15.1±1.9 years in Arm 2 (p=0.27), and with 65.2% males in Arm 1 and 66.6% males in Arm 2 (p=0.76). Forty of 46 patients (87%) in Arm 1 and 46 of 48 patients (92%) in Arm 2 completed all 12 months of treatment. Reasons for discontinuation were skin infection and pain at infusion sites in Arm 1,and decrease in SF < 1000 μg/ L in Arm 2.Efficacy findings: Table 1 shows the changes in SF, LIC, and cardiac MRI values at baseline and at completion of 1 year on therapy.Median SF μg/ LMean LIC mg/gmMedian Cardiac MRI msecArm 1n=40Baseline: 4355P:0.04n=36Baseline: 14.5 ±2.6P:0.4n=36Baseline: 15.4P:0.031 Year: 31541 Year: 9.1 ± 1.91Year: 19.5P: < 0.001P: <0.001P: < 0.001Arm 2n=46Baseline: 4654n=40Baseline: 14.1 ±2.6n=40Baseline: 15.81 Year: 28761 Year: 10.3± 2.21 Year: 21.1P: < 0.001P: < 0.001P: < 0.001Safety findings: No serious adverse events were reported during the study in either treatment group. The number of adverse effects reported was comparable in both arms. Compliance: Treatment compliance was significantly higher in Arm 2 than in Arm 1(95% vs. 80%, respectively<0.001). Satisfaction: Significantly more patients in Arm 2 than in Arm 1 reported being satisfied with treatment at both 6 months (92% vs. 64%, respectively; p<0.001) and 12 months (88% vs. 59%, respectively; p<0.001). QoL: Improvement in QoL was seen in significantly more patients in Arm 2 than in Arm 1 (85% vs. 60%, respectively; p<0.001). ConclusionData from this randomized prospective study show that while both forms of combination therapy, DFP with DFX and DFP with DFO, were effective in reducing iron overload in multi-transfused β-thalassemia major, patients who received DFP and DFX showed a higher decline in serum ferritin, greater improvement in cardiac T2*, higher treatment satisfaction, better compliance, and more improvement in QoL than did patients who received DFP and DFO, with no increased toxicity. Disclosures:No relevant conflicts of interest to declare.

Assessment and management of iron overload in β‐thalassaemia major patients during the 21st century: a real‐life experience from the Italian Webthal project

We conducted a cross-sectional study on 924 β-thalassaemia major patients (mean age 30·1 years) treated at nine Italian centres using the WEBTHAL software, to evaluate real-life application of iron overload assessment and management standards. Serum ferritin <2500 ng/ml was a risk factor for never having liver iron concentration (LIC) measurement, while absence of cardiac disease and siderosis were risk factors for a delay in LIC measurement >2 years. Patients who never had a cardiac MRI (CMR) T2* measurement were <18 years, had iron intake ≤0·4 mg/kg per day, or a serum ferritin <2500 ng/ml. A history of normal CMR T2* was the main risk factor for a delay in subsequent assessment of >2 years. Deferoxamine (22·8%) was more commonly used in patients with Hepatitis C Virus or high serum creatinine. Deferiprone (20·6%) was less commonly prescribed in patients with elevated alanine aminotransferase; while a deferoxamine + deferiprone combination (17·9%) was more commonly used in patients with serum ferritin >2500 ng/ml or CMR T2* <20 ms. Deferasirox (38·3%) was more commonly prescribed in patients <18 years, but less commonly used in those with heart disease or high iron intake. These observations largely echoed guidelines at the time, although some practices are expected to change in light of evolving evidence.

Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.