Stratification for Age in Transfusion-Dependent Thalassemia

Abstract Introduction. Transfusion-dependent β-thalassemia (TDT) is the most severe clinical form of β-thalassemia and requires regular long-term red cell transfusions for survival. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in TDT patients. Methods. We considered all TDT patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project at the first MRI examination. Iron concentrations were measured by T2* multiecho technique. All complications were classified according to international guidelines. Results. Three groups of patients were identified: age<12 years (group 0, N=53), age between 12-17 years (group 1, N=100) and age≥18 years (group 2, N=1857). The number of transfusional units in the 12 months before the MRI scan resulted significantly lower in group 0 versus both group 1 (20.8±5.3 vs 34.8±10.6; P<0.0001) and group 2 (20.8±5.3 vs 39.2±10.9; P>0.0001) and in group 1 versus group 2 (P=0.021). The Table shows the comparison of clinical characteristics among the 3 groups. Serum ferritin levels were significantly higher in both groups 0 and 1 when compared to group 2. Liver aminotransferases were significantly lower in group 1 than in group 2. The number of patients with MRI LIC (liver iron concentration) >3 mg/g dw was significantly higher in group 1 than in group 2 and the number of patients with global heart T2*<20 ms was significantly lower in group 0 than in group 2. Among the endocrinopathies, hypogonadism, hypothyroidism and osteoporosis were significantly less frequent in groups 0 and 1 than in group 2 while diabetes was significantly less frequent only in group 1 when compared to group 2. Frequency of heart failure was comparable among the groups while the frequency of arrhythmias was significantly lower in group 1 than in group 2. The types of chelation regimens were significantly different among groups (<0.0001) (see Figure). Conclusions. Younger patients had more hepatic iron, despite the significant lower transfusional burden. Cardiac iron overload occurs early in TDT patients but it is more frequent in older patients. Endocrinopathies (excluding diabetes) and cardiac complications become clinically evident during the second decade and are time-dependent processes. Our data suggest the need for an effective strategy to prevent iron overload since early childhood, in order to reduce its toxic effect and prevent the development of long-term complications. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

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Deferiprone Has a Dose-Dependent Effect on Liver Iron Concentration

Blood ◽

10.1182/blood.v126.23.2159.2159 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2159-2159 ◽

Cited By ~ 1

Author(s):

Alessia Pepe ◽

Tommaso Casini ◽

Liana Cuccia ◽

Francesco Sorrentino ◽

Rosamaria Rosso ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron Concentration ◽

Liver Iron ◽

Hepatic Iron Overload ◽

Group 2 ◽

Dose Dependent ◽

Dose Dependent Effect ◽

Group 1

Abstract Purpose: The aim of this multi-centre study was to retrospectively assess in thalassemia major (TM) if deferiprone (DFP) had a dose-dependent effect on liver iron concentration (LIC) assessed by quantitative magnetic resonance imaging (MRI). Methods: Among the 958 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we identified hose with an MRI follow up study at 18±3 months who had been received DFP monotherapy and had no changes in dose of DFP between the 2 MRI scans. Patients were divided into two groups according to the DFP dose: 79 patients with ≤ 75 mg/kg/d (group 1) and 39 with > 75 mg/kg/d (group 2). Hepatic iron overload was measured by the T2* multiecho technique and T2* values were converted into LIC values using the calibration curve introduced by Wood et al. Results: The two groups had comparable baseline MRI LIC values. The table shows the evolution of different iron overload risk classes between the baseline and the FU MRI. The percentage of patients that worsened their status was significantly higher in group 1 than in group 2 (26.6% vs 7.7%; P=0.016). Subgroup analysis in patients with hepatic iron overload at baseline (MRI LIC > 3mg/g/dw) was conducted: 48 patients from group 1 (DFP dose: mean 70.6±11.2 mg/kg/d, median 75 mg/kg/d) and 30 from group 2 (DFP dose: mean 85.2±6.6 mg/kg/d, median 84 mg/kg/d). The two subgroups had comparable baseline MRI LIC values (10.2±8.1 mg/g dw vs 11.1±8.7 mg/g dw (P=0.314). While the mean change in subgroup 2 ( -1.8±6.3mg/g/dw, P=0.131) was more favourable than in subgroup 1 (+0.1±7.7 mg/g/dw, P=0.903), the change in MRI LIC values did not reach statistical significance between the two subgroups (P=0.579) (Figure 1), which may be due to small cohort evaluated. Conclusions: In TM patients the worsening in MRI LIC can be prevented by increasing the dose of deferiprone above the widely used regimen of 75 mg/kg body weight. Our results are consistent with the iron balance studies performed by Grady RW et al. Table 1. Evolution of different iron overload risk classes between the baseline and the FU MRI. The underlined numbers represent the patients who remained in the same risk class. DFP dose ≤ 75 mg/kg/d (N=79) FU LIC <3 mg/g dw 3-7 mg/g dw 7-15 mg/g dw ≥15 mg/g dw Baseline LIC <3 mg/g dw (N=31) 21 7 3 0 3-7 mg/g dw (N=22) 10 4 6 2 7-15 mg/g dw (N=14) 0 6 5 3 ≥15 mg/g dw (N=12) 1 0 5 6 Total at the FU 32 17 19 11 DFP dose > 75 mg/kg/d (N=39) FU LIC <3 mg/g dw 3-7 mg/g dw 7-15 mg/g dw ≥15 mg/g dw Baseline LIC <3 mg/g dw (N=9) 6 2 1 0 3-7 mg/g dw (N=14) 3 11 0 0 7-15 mg/g dw (N=8) 0 4 4 0 ≥15 mg/g dw (N=8) 1 0 2 5 Total at the FU 10 17 7 5 Figure 1. Changes of MRI LIC values in patients with basal MRI LIC > 3 mg/g/dw. Figure 1. Changes of MRI LIC values in patients with basal MRI LIC > 3 mg/g/dw. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

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MRI Prospective Survey on Cardiac and Hepatic Iron in Thalassemia Intermedia Patients Treated with Desferrioxamine, Deferiprone and Deferasirox

Blood ◽

10.1182/blood.v124.21.4041.4041 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4041-4041

Author(s):

Antonella Meloni ◽

Aurelio Maggio ◽

Anna Pietrapertosa ◽

Pier Paolo Bitti ◽

Sabrina Armari ◽

...

Keyword(s):

Iron Overload ◽

Iron Concentration ◽

Iron Chelation ◽

Hepatic Iron ◽

Thalassemia Intermedia ◽

Liver Iron ◽

Cardiac Iron ◽

Number Of Patients ◽

Mri Scans ◽

Magnetic Resonance Imaging Mri

Abstract Background. Few studies have evaluated the efficacy of iron chelation therapy in thalassemia intermedia (TI) patients. Our study aimed to prospectively assess by quantitative Magnetic Resonance imaging (MRI) the efficacy of the three available chelators in monotherapy in transfusion dependent (TD) TI patients. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 103 TI patients TD with an MRI follow-up (FU) study at 18±3 months who had been received one chelator alone between the two MRI scans. Iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO – mean dosage 37.52±8.69 mg/kg/die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFP– dosage 71.70±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX – mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73±15.89 years. At baseline in DFO group two patients (7.4%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. At baseline in DFP group two patients (8.7%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. All the 5 patients (35.7%) under DFX therapy with pathological global heart T2* at the baseline remained at the same status at the FU. The percentage of patients who maintained a normal global heart T2* value was comparable for DFO (100%), DFP (100%) and DFX (88.9%) groups (P=0.164). Among the 46 patients with hepatic iron at baseline (MRI LIC ≥3 mg/g/dw), the reduction in the MRI LIC values was significant only in the DFO group (DFO: -3.39±6.38 mg/g/dw P=0.041; DFP: -2.25±6.01 mg/g/dw P=0.136 and DFX: -0.36±5.56 mg/g/dw P=0.875). The decrease in MRI LIC values was comparable among the groups (P=0.336). The number of patients with a MRI LIC<3 mg/g/dw went up from 10 (37%) to 11 (40.7%) in the DFO group, from 6 (26.1%) to 8 (34.8%) in the DFP group and from 2 (14.3%) to 8 (57.1%) in the DFX group. The percentage of patients who maintained a normal MRI LIC value was comparable for DFO (90%) vs DFP (50%) and DFX (100%) groups (P=0.191). Conclusion: Prospectively in transfusion-dependent TI patients at the dosages used in the clinical practice, DFO and DFP showed 100% efficacy in maintaining a normal global heart T2* value while DFX had 100% efficacy in maintaining a normal LIC value. Further prospective studies involving more patients with iron at the baseline are needed to establish which is the most effective drug in reducing iron levels. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

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Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms19124070 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4070 ◽

Cited By ~ 4

Author(s):

Antoine Finianos ◽

Charbel Matar ◽

Ali Taher

Keyword(s):

Hepatocellular Carcinoma ◽

Iron Overload ◽

Treatment Success ◽

Iron Concentration ◽

Iron Chelation ◽

Multicenter Studies ◽

Major Life ◽

Liver Iron ◽

Magnetic Resonance Imaging Mri ◽

Personalized Approach

With the continuing progress in managing patients with thalassemia, especially in the setting of iron overload and iron chelation, the life span of these patients is increasing, while concomitantly increasing incidences of many diseases that were less likely to show when survival was rather limited. Hepatocellular carcinoma (HCC) is a major life-threatening cancer that is becoming more frequently identified in this population of patients. The two established risk factors for the development of HCC in thalassemia include iron overload and viral hepatitis with or without cirrhosis. Increased iron burden is becoming a major HCC risk factor in this patient population, especially in those in the older age group. As such, screening thalassemia patients using liver iron concentration (LIC) measurement by means of magnetic resonance imaging (MRI) and liver ultrasound is strongly recommended for the early detection of iron overload and for implementation of early iron chelation in an attempt to prevent organ-damaging iron overload and possibly HCC. There remain lacking data on HCC treatment outcomes in patients who have thalassemia. However, a personalized approach tailored to each patient’s comorbidities is essential to treatment success. Multicenter studies investigating the long-term outcomes of currently available therapeutic options in the thalassemia realm, in addition to novel HCC therapeutic targets, are needed to further improve the prognosis of these patients.

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Longitudinal analysis of heart and liver iron in thalassemia major

Blood ◽

10.1182/blood-2008-04-148767 ◽

2008 ◽

Vol 112 (7) ◽

pp. 2973-2978 ◽

Cited By ~ 123

Author(s):

Leila J. Noetzli ◽

Susan M. Carson ◽

Anne S. Nord ◽

Thomas D. Coates ◽

John C. Wood

Keyword(s):

Longitudinal Analysis ◽

Time Lag ◽

Iron Concentration ◽

Thalassemia Major ◽

Iron Accumulation ◽

Liver Iron ◽

Cross Sectional ◽

Cardiac Iron ◽

Cardiac Iron Overload ◽

Magnetic Resonance Imaging Mri

Abstract High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.

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Myocardial and Hepatic Iron Overload and Cardiac Function In Sickle/Thalassemia Patients Of Italian Origin

Blood ◽

10.1182/blood.v122.21.2252.2252 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2252-2252

Author(s):

Antonella Meloni ◽

Giovan Battista Ruffo ◽

Daniele De Marchi ◽

Antonio Cardinale ◽

Anna Pietrapertosa ◽

...

Keyword(s):

Cardiac Function ◽

Iron Overload ◽

Conflicts Of Interest ◽

Iron Concentration ◽

Hepatic Iron ◽

Liver Iron ◽

Hepatic Iron Overload ◽

The Mean ◽

Magnetic Resonance Imaging Mri ◽

Italian Origin

Abstract Introduction Sickle-thalassemia results from the combined heterozygosity for sickle-cell and β-thalassemia genes. This study evaluates myocardial and hepatic iron overload and cardiac function in Italian patients and explores their correlation with transfusions, age and sex. Methods Fifty-nine sickle-thalassemia patients (29 males, mean age 35.6±14.1 years), enrolled in the MIOT network underwent magnetic resonance imaging (MRI). T2* value for all 16 myocardial segments and global heart T2* value were calculated. Hepatic T2* value was converted into liver iron concentration (LIC). Cine images were acquired to quantify biventricular volumes and ejection fraction (EF). Results 55 (93%) patients had all segmental T2* values normal (>20 ms). Of the 4 patients with abnormal segmental T2* values, all showed an heterogeneous myocardial iron overload (some segments with T2*>20 ms and other with T2*<20 ms) and only one had a global T2*<20 ms. The mean global heart T2* value was 34.4±6.2 ms. The mean LIC was 5.9±6.5 mg/g/dw and 30 patients (50.8%) had a pathological value (≥ 3 mg/g dw). There was a statistically significant positive correlation between global heart T2* and age but with poor linearity (R=0.368; P=0.004) and there was not a significant correlation between age and LIC. Males and females had comparable global heart T2* values and LIC values. Twenty patients were regularly transfused, 32 received sporadic transfusions while 7 were not transfused. The comparison among the three groups is shown in Table 1. We did not find significant differences in the global heart T2* value while patients regularly transfused had significantly higher LIC than sporadically transfused patients. Biventricular volumes indexed by body surface area and ejection fractions were comparable among the groups. Conclusions In respect of MIO, the sickle/thalassemia patients are similar to patients with homozygous SCD for which iron overloading is relatively rare. Hepatic iron overload may develop also in no regularly-transfused patients, maybe due to increased absorption of iron from the digestive tract, characteristic of both SCD and thalassemia intermedia patients. This finding underlines the importance to monitor by MRI also no regularly transfused sickle/thalassemia patients. Disclosures: No relevant conflicts of interest to declare.

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Efficacy of deferasirox in reducing and preventing cardiac iron overload in β-thalassemia

Blood ◽

10.1182/blood-2009-04-217455 ◽

2010 ◽

Vol 115 (12) ◽

pp. 2364-2371 ◽

Cited By ~ 119

Author(s):

Dudley J. Pennell ◽

John B. Porter ◽

Maria Domenica Cappellini ◽

Amal El-Beshlawy ◽

Lee Lee Chan ◽

...

Keyword(s):

Iron Overload ◽

Iron Reduction ◽

Geometric Mean ◽

Iron Concentration ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Liver Iron ◽

Ventricular Ejection Fraction ◽

Cardiac Iron ◽

Cardiac Iron Overload

Cardiac iron overload causes most deaths in β-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with β-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean ± coefficient of variation) improved from a baseline of 11.2 ms (± 40.5%) to 12.9 ms (± 49.5%) (+16%; P < .001). LVEF (mean ± SD) was unchanged: 67.4 (± 5.7%) to 67.0 (± 6.0%) (−0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (± 25.6%) to 32.5 ms (± 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (± 4.7%) to 69.6 (± 4.5%) (+1.8%; P < .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.

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Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis

Acta Haematologica ◽

10.1159/000494487 ◽

2018 ◽

Vol 141 (1) ◽

pp. 32-42 ◽

Cited By ~ 5

Author(s):

Huihong Dou ◽

Yuanhan Qin ◽

Guoli Chen ◽

Yanjun Zhao

Keyword(s):

Iron Overload ◽

Meta Analysis ◽

Compliance Rate ◽

Iron Concentration ◽

Similar Efficacy ◽

Biomedical Literature ◽

Liver Iron ◽

Randomized Controlled Studies ◽

Gastrointestinal Problems

Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (>30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.

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Hepatic iron load differs strikingly between peritoneal dialysis and hemodialysis patients

Bulletin de la Dialyse à Domicile ◽

10.25796/bdd.v2i4.23613 ◽

2019 ◽

Vol 2 (4) ◽

pp. 181-191

Author(s):

Guy Rostoker ◽

Mireille Griuncelli ◽

Nasredine Ghali ◽

Séverine Beaudreuil ◽

Yves Cohen ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Iron Overload ◽

Iron Concentration ◽

Dry Weight ◽

Hemodialysis Patients ◽

Hepatic Iron ◽

Dialysis Patients ◽

Liver Iron ◽

Iron Load ◽

Magnetic Resonance Imaging Mri

Introduction Iron overload is one of the most controversial topics in the management of anemic dialysis patients. Parenteral iron supplementation is commonly prescribed to hemodialysis (HD) patients but less frequently to peritoneal dialysis (PD) patients. Moreover, ferritin targets are far lower and more physiological in PD than in HD. Methods We compared the liver iron concentration (LIC) measured by means of Signal-Intensity ratio (SIR) magnetic resonance imaging (MRI) according to Rennes University method in a cohort of 32 PD patients living in the Paris region published in 2017, with two cohorts of French HD patients studied in the same way (119 patients reported in 2012 and 80 further patients reported in 2014). Results Normal hepatic iron load (LIC ≤ 50 µmol/g of dry weight) was observed in 81.3% of the 32 PD patients (CI: 64.3-91.5%), as compared to only 16% (CI: 10.4-23.7%) in the first HD cohort and 35% (CI: 25.4-45.9%) in the second HD cohort (p<0.0001 for both comparisons; X2 test). Mild iron overload (50 < LIC ≤ 100 µmol/g) was found in 5 PD patients and severe overload (LIC > 200 µmol/g) in only one PD patient (who had received IV iron) (3.1%; CI: 0-17.1%). Conversely, severe iron overload was found in 30.3% of patients in the first HD cohort (CI: 22.7-39%) and 11.3% of those in the second HD cohort (CI: 5.8-20.2%) (p= 0.0033 versus the first HD cohort, X2 test). Conclusion Contrary to hemodialysis patients, iron overload is rare and mostly mild in peritoneal dialysis patients.

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POSTERIOR SPINAL INSTRUMENTATION FOR TUBERCULOSIS SPONDYLITIS

Hirurgiâ pozvonočnika ◽

10.14531/ss2006.2.48-54 ◽

2006 ◽

pp. 048-054

Author(s):

Aleksandr Yuryevich Mushkin ◽

Dmitry Vladimirovich Kuklin ◽

Mikhail Viktorovich Belyakov ◽

O. V. Dolenko

Keyword(s):

Posterior Instrumentation ◽

Spinal Instrumentation ◽

Posterior Fixation ◽

Anterior Fusion ◽

Spinal Reconstruction ◽

Number Of Patients ◽

Group 3 ◽

Group 2 ◽

Group 1

Objective. To study potentialities of posterior instrumentation for treatment of TB spondylitis in adults. Material and Methods. Data on the treatment outcomes of 93 adult patients with TB spondylitis at T2–L5, which underwent radical reconstructing and restorative surgeries in the period of active inflammatory process were analyzed. In 40 cases a traditional technique was used (Group 1); in 11 cases this technique was supplemented by posterior fixation with Harrington rods or CITO-plates (Group 2) and in 42 – with CDI (Group 3). Deformity dynamics, character of complications, and changes in neural disorders and pain dynamics defined the operative effect. Results. The absence of instrumented fixation in Group 1 was accompanied with the most significant decrease in graft sizes and most numerous complications in a zone of anterior fusion. Both these characteristics have least values in Group 3. Use of conventionally semi-rigid constructs in Group 2 caused 7 complications in a zone of posterior fixation out of 11 cases (66.4 %). There were 2 complications out of 42 cases (4.3 %) in Group 3. Short-term pain intensity decrease was achieved in all groups. However augmenting of pain syndrome was registered in a considerable number of patients in Groups 1 and 2 in a long-term period, while there were no negative long-term outcomes in Group 3. Conclusion. Combination of radical spinal reconstruction and fixation with segmented instrumentation of the third generation for TB spondylitis provides considerable improvement of treatment results and reduction of rehabilitation and in-hospital periods.

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Optimizing Iron Chelator Treatment in Cardiac and Hepatic Siderosis: Efficacy of Divided Deferasirox (EXJADER) – Doses

Blood ◽

10.1182/blood.v118.21.2110.2110 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2110-2110

Author(s):

Regine Grosse ◽

Andrea Jarisch ◽

Jin Yamamura ◽

Peter Nielsen ◽

Roland Fischer ◽

...

Keyword(s):

Iron Overload ◽

Treatment Period ◽

Iron Concentration ◽

Iron Chelator ◽

Liver Iron ◽

Once Daily ◽

Cardiac Iron ◽

Cardiac Siderosis ◽

Cardiac Iron Overload ◽

The Mean

Abstract Abstract 2110 Introduction: Iron chelation is the life-saving therapy in patients with chronic transfusion therapy. Treatment with deferoxamine, deferiprone or deferasirox has dramatically improved the life expectancy, but still myocardial siderosis and hepatic siderosis is cause of morbidity and mortality in regularly transfused patients with ß-thalassemia major (TM) or Diamond-Blackfan Anemia (DBA). Deferasirox (DSX) a once-daily oral iron chelator has demonstrated efficacy in reducing hepatic iron and body iron burden, as well as cardiac iron. But in patients with severe cardiac siderosis (T2* ≤ 10ms) a combination therapy with deferiprone (Ferriprox®) and deferoxamine (Desferal®) is the recommended therapy. However, some patients will not benefit from this treatment due to unacceptable toxicity, poor response or noncompliance. Method: We tested a twice-daily deferasirox (Exjade®) -dose with special respect to its efficacy on reducing cardiac iron overload. A group of six patients with severe secondary siderosis was studied, TM (n=5) and DBA (n=1), (5 females, age 8–37 years, mean age 27.7 years). In all patients the liver iron concentration was measured repeatedly by SQUID biosusceptometry or by magnetic resonance imaging (MRI) using the MRI-R2 technique (St. Pierre et al, 2005). In 4 patients with severe cardiac siderosis (T2* ≤ 10ms) we also followed the cardiac iron concentration by MRI using a single breath-hold, multi-echo T2* method. Patients received a daily DSX dose of 19 mg/kg/d – 45 mg/kg/d, with a mean dose of 32 mg/kg/d. Results: The mean initial liver iron concentration of 2.7 mg/g-liver (0.96 – 5.5mg/g) decreased to 1.5 mg/g-liver (0.6 – 3.9 mg/g). The mean monthly liver iron clearance was 6.8%/month (1.7 – 16.8%/month) in a treatment interval of 4 – 26 months (mean: 9.8 months), the patients demonstrated a significant liver iron reduction of 44.4%. The mean serum ferritin was reduced from 3048 μg/l to 1786 μg/l. The mean monthly cardiac iron clearance was 3.1%/month (1.2 – 4.7%/month) and the mean T2* value improved from 9.5 ms to 14.3 ms (+50%). We showed a substantial improvement in patients with severe cardiac siderosis with a T2* improvement of 50 % after a mean treatment period of 12 months with a mean DSX dose of 32 mg/kg/d. In comparison, an improvement of 23.8% was found in 6 patients with T2* < 10 ms, after a treatment period of 18 months with a once daily DSX mean dose of 38 mg/kg/d (Pathare et al, 2010). Other authors reported an improvement of 10.8% in 47 patients (T2* < 10 ms, treatment period 12 months) with a once daily DSX mean dose of 32 mg/kg/d (Pennell et al, 2009). No severe side effects were seen in our patients and only minor increases in creatinine values, which were reversible with dose reduction. Conclusion: Deferasirox divided in twice daily doses is a safe and effective therapy for patients with severe cardiac iron overload (T2* < 10ms) or hepatic iron overload, who do not well tolerate a combination therapy with deferiprone and deferoxamine. Disclosures: Off Label Use: Deferasirox (Exade)is given instead of a once daily dose, in a twice daily divided dose. The daily dose of Deferasirox is in recommended range.

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