Deferiprone Oral Solution, An Alternative for Early Chelation Therapy In Young Children with Transfusional Iron Overload: A Preliminary Data From A 6-Month Study Period

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2108-2108
Author(s):  
Duantida Songdej ◽  
Nongnuch Sirachainan ◽  
Pakawan Wongwerawattanakoon ◽  
Praguywan Kadegasem ◽  
Ampaiwan Chuansumrit
Keyword(s):  
Young Children ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Oral Solution ◽  
Tablet Form ◽  
Iron Load ◽  
Short Period ◽  
Hbh Disease

Abstract Abstract 2108 Introduction: The choice of chelation therapy is limited in young children with transfusional iron overload. Desferrioxamine can disturb bone growth especially in those younger than 6 years of age. Moreover, incooperation of young patients to subcutaneous overnight infusion of the medication causes none adherence. Deferasirox is an unaffordable chelation for many patients in developing countries. Deferiprone has been evaluated in several studies for its safety and efficacy in young children. However, the widely used large tablet form of deferiprone may not be suitable for this group of patients. Objective: To study efficacy, safety and tolerability of deferiprone oral solution for early chelation therapy in young children with transfusional iron overload. Inclusion criteria: Patients age <10 years with transfusional iron overload (ferritin >1,000 ng/mL or received >10 transfusions) at Pediatrics Department, Faculty of Medicine, Ramathibodi Hospital, Mahidol University that fail to accomplish adequate chelation by desferrioxamine or deferiprone tablet due to poor compliance. Methods: Deferiprone oral solution (Ferriprox®) was given at a dose of 75 mg/kg/day in three divided dose for patients who previously received tablet form of deferiprone and 50 mg/kg/day for others who never experienced deferiprone. Ferritin level, complete blood counts, alanine transferase, serum creatinine and spot urine protein were measured every 4 weeks. Complete history taking and physical examination were performed and compliance was recorded during monthly visit. Results: A total of 10 patients were enrolled with equal male and female. The median age was 4.8 years (range 2–9.8 years) whereas seven patients was ≤5 years of age. Seven out of 10 patients were diagnosed β thalassemia HbE disease and the rest were diagnosed β thalassemia major, HbH disease and hereditary spherocytosis respectively. Only one patient was splenectomized and none of them was seropositive for hepatitis B or C virus. All patients have received regular packed red cell transfusion for the median of 3.9 years (range 1.1–6.4 years) to maintain pretransfusion hematocrit of 27%. The median transfusional iron load was 0.39 mg/kg/day (range 0.29–0.48 mg/kg/day) whereas the median ferritin level at the beginning of the study was 1,598.2 ng/mL (range 654.4–3, 163.8 ng/mL). Two patients were previously chelated with desferrioxamine, three patients with deferiprone tablet and 1 with combined desferrioxamine and deferiprone tablet. The remaining four patients were naïve for deferiprone oral solution. Efficacy The median ferritin level at the end of 6 months was significantly lower than that of pretreatment period (median 1,445.8 ng/mL, range 114.6–2806.2 ng/mL, p=0.037). Four out of 10 patients had final ferritin level at 6 months <1,000 ng/mL and half of them had ferritin level <500 ng/mL. This group of four patients were ≤5 years old and had ferritin level between 654.4–1, 507.8 ng/mL at the beginning of study. However, the transfusional iron load was ranging from 0.36–0.48 mg/kg/day. They all received 50 mg/kg/day of deferiprone solution. One out of these four was a patient with HbH disease who was occasionally transfused. The ferritin level of the boy decreased from 654.4 ng/mL to 114.6 ng/mL and deferiprone oral solution could be stopped at the end of the third month. Safety No episode of neutropenia or agranulocytosis occurred. One patient had an episode of mild thrombocytopenia of 137,000/μL during the second month of treatment. However, deferiprone oral solution was continued and spontaneous recovery of platelet counts was observed on the following month. No transaminitis and renal impairment were found. Neither arthralgia nor GI discomfort occurred. Tolerability All patients tolerated well with deferiprone oral solution and excellent compliance of the treatment was achieved. Conclusion: Deferiprone oral solution is a safe and effective alternative for chelation therapy in transfusion-related iron overload especially those with younger age. Serum ferritin level decreased well in a short period of time with only as low dose of deferiprone as 50 mg/kg/day when given at earlier age with starting ferritin level ≤1,000 ng/mL. Better absorption of deferiprone in the form of solution may be a reason for such efficacy. Moreover, liquid formulation of the medication could be a solution to improve adherence to chelation treatment in young children. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1136-1142 ◽  
Author(s):  
HC Kim ◽  
NP Dugan ◽  
JH Silber ◽  
MB Martin ◽  
E Schwartz ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Cell Disease ◽  
Donor Blood ◽  
Iron Load ◽  
Blood Usage ◽  
Hb S

Abstract Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

The Tolerability, Safety and Efficacy of a New Oral Solution of Deferiprone in Children with Transfusional Iron Overload

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5373-5373
Author(s):  
Mohsen Saleh El-Alfy ◽  
Teny Tjitra Sari ◽  
Lee Lee Chan ◽  
Fernando Tricta ◽  
Amal El-Beshlawy
Keyword(s):  
Young Children ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Neutrophil Count ◽  
Older Patients ◽  
Adverse Reactions ◽  
Oral Solution ◽  
Tablet Formulation ◽  
Limiting Factor ◽  
Safety And Efficacy

Abstract Although there are 20 yr of clinical experience with deferiprone in treating transfusional iron overload, limited data exist on the safety and efficacy of deferiprone in very young children. Difficulties in swallowing the tablet formulation of deferiprone (Ferriprox®, ApoPharma, Canada), is a limiting factor in the administration of deferiprone in young children. The current study evaluated the tolerability, safety and efficacy of a new liquid formulation of deferiprone (Ferriprox® Oral Solution) in iron-overloaded pediatric patients with transfusion-dependent anemias (≥ 8 transfusions/year). The study also assessed the daily neutrophil count in patients who continued deferiprone therapy during episodes of mild neutropenia. The study was approved by the relevant regulatory authorities and ethics review boards. Informed consent was obtained from the patients’ legal representatives. One-hundred children [91Thal major, 8 HbE, 1 Sickle Cell disease; 46 female and 54 male; 76 Caucasian (Egyptian), 24 Asian (9 Chinese, 13 Indonesian, 2 Malay)] ranging from 1 to 10 yr of age (median 5.0 yr) were enrolled. At enrollment, 51 children were being treated with deferoxamine (mean duration 1.82 ± 1.95 years; range 0.1–7.3 yr), 20 with deferiprone (mean duration 0.5 ± 0.6 yr; range 0. 04–2 yr), 8 patients with deferasirox (mean duration 0.4 ± 0.5 yr; range 0.1–1.6 yr) and 21 patients were naïve to chelation therapy. Deferiprone therapy was initiated at 50 mg/kg/day, divided in 3 doses, for the first 2 weeks, and then increased to 75 mg/kg/day. The dose was further increased to 100 mg/kg/day for those patients with ferritin &gt; 2500 μg/L at baseline. Ninety-five children completed 6 months of therapy. One patient was lost to follow-up, 2 patients voluntarily withdrew consent (1 patient disliked the taste, 1 patient did not comply with weekly visits), and 2 were withdrawn due to adverse events. Therapy with the oral solution of deferiprone was not associated with unexpected adverse reactions. The incidence of gastrointestinal adverse reactions was lower than observed for the tablet formulation in older patients (Table). Oral solution in children ≤ 10 yr old Tablet formulation in children &gt; 6 yr old and adults Adverse Reaction (AR) % Patients with AR % Patients with AR Nausea 1% 16% Abdominal Pain 6% 14% Vomiting 6% 12% Arthralgia 4% 11% Neutropenia (0.5 × 109/L ≤ ANC &lt; 1.5 × 109/L) 6% 6% Agranulocytosis (0.5 &lt; ANC) 2% 1% Five patients experienced single episodes of mild neutropenia [absolute neutrophil count (ANC) 1.5 × 109/L but not less than 1.0 × 109/L], which resolved and did not recur, despite continuous deferiprone use. Another patient experienced 2 transient episodes of mild neutropenia and a third episode that progressed to agranulocytosis (ANC &lt; 0.5 × 109/L). Deferiprone was discontinued and the patient was treated with G-CSF. The event resolved (ANC &gt; 1.5 × 109/L) within 9 days upon discontinuation of deferiprone. Another patient experienced a single episode of agranulocytosis, which resolved within 9 days upon discontinuation of deferiprone and therapy with G-CSF. During the 6-month therapy, there was a significant decrease in serum ferritin from a mean baseline value of 2532 ± 1463 to 2176 ± 1144 μg/L (p&lt; 0.0005). The new oral solution of deferiprone was well tolerated and effective in lowering serum ferritin in young children with transfusion dependent anemias and exhibited a safety profile similar or better to that reported for the tablet formulation in older patients. The results also suggest that not all episodes of mild neutropenia progress to agranulocytosis with continued deferiprone therapy, and that further studies are warranted to differentiate those patients from those at risk of developing deferiprone-induced agranulocytosis following neutropenia. This study includes the first report of patients using deferiprone as their first iron chelator.

Efficacy of ICT with Deferasirox in Transfusional Iron Overloaded Patients with MDS or AA.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3810-3810 ◽  
Author(s):  
June-Won Cheong ◽  
Hyeoung-Joon Kim ◽  
Kyoo-Hyung Lee ◽  
Sung-Soo Yoon ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin Level ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Dry Weight ◽  
Progressive Increase ◽  
Mean Value ◽  
Serial Measurement ◽  
Baseline Values

Abstract Abstract 3810 Poster Board III-746 PURPOSE Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). The clinical data on specific benefits of deferasirox in transfusion-related iron overload patients with MDS or AA has been limited. METHODS: We have prospectively investigated the efficacy of deferasirox by serial measurement of s-ferritin level and LIC by R2-MRI in transfusional iron overload patients with MDS or AA. RESULTS: A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. Mean value of s-ferritin level in enrolled patients was 4,788 ng/ml in MDS and 4,188 ng/ml in AA at the time of deferasirox initiation. Mean value of LIC was 24.4 mg Fe/g dry weight in MDS and 22.4 mg Fe/g dry weight in AA. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients and was withheld If the s-ferritin falls below 500 ng/ml. Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 12 months of medication, s-ferritin level significantly decreased by 1824.0 ng/ml form baseline values, a reduction of 38.1% for patients with MDS (p<0.0001) and significantly decreased by 3559.1 ng/ml (85.0%) for patients with AA (p<0.0001). LIC decreased by 11.2 mg Fe/g dry weight, a reduction of 35.7% for patients with MDS, and significantly decreased by 8.1 mg Fe/g dry weight, a reduction of 27.6% for patients with AA (p=0.0028). The patients with lower transfusional requirements (<4 units/month) during the study showed significantly more reduction of LIC level than those with higher requirements (≥4 units/month) (35.7% vs. 2.8%; p<0.0001). The most common drug-related adverse events (AE) were gastrointestinal disturbances and non-progressive increase in s-creatinine, however, AE were transient and mild-to-moderate in severity. All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). CONCLUSION: Deferasirox is effective in reducing LIC and s-ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Disclosures: No relevant conflicts of interest to declare.

Iron Chelation Therapy in Transfusion Dependent Patients with Thalassemia and Minimal Liver Iron Load

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4270-4270
Author(s):  
Antonios Kattamis ◽  
Konstantinos Stokidis ◽  
Theoni Petropoulou ◽  
Dimitra Kyriacopoulou ◽  
Polyxeni Delaporta ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Iron Overload ◽  
Research Funding ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Iron Load ◽  
Low Levels

Abstract Abstract 4270 Background: Recent advances in the treatment of iron overload in patients with transfusion- dependent thalassemia have dramatically changed iron related morbidity and mortality. Intensive chelation therapy by using combination therapy or monotherapy at high doses had led to total clearing of the iron in many patients. The best approach for chelation treatment in patients with low levels of iron overload is debatable. Patients and Methods This study included all the patients with thalassemia major with minimal liver iron overload, followed in our unit. More precisely, to be eligible for this observational study, the patients needed to have liver iron concentration (LIC) <1.5 mg Fe/gram dry weight tissue, defined by MRI, and to have at least a subsequent MRI evaluation after this time. The mean observation time, which was the time between the two MRIs, was 16.9±5.2 months. Results Fourty five patients (22 females, 30 non-splemectomized, 21 HCV seropositive, mean age: 31±5.6 years) have reached minimal levels of iron overload in any time point after 2004. Thirty one of them have been treated with combined therapy of desferrioxamine (DFO) and deferiprone (DFP) and 5, 6 and 3 with monotherapy of deferasirox (DFX), DFP and DFO, respectively. After reaching these levels, 42% of the patients changed therapy, with the most frequent change being from combined therapy to monotherapy (15 patients). Baseline ferritin levels at the time of the first MRI range from 43 to 4336 ng/ml (median 230 ng/ml) and they were not affected by spleen, gender or HCV status. Baseline LIC (mean 1.2 ± 1.7 mgFe/g.d.w.) correlated well with ferritin levels (Spearman's rho = 0.47, p<0.005), as did ferritin changes to LIC changes (Spearman's rho = 0.67, p<0.005). The results on the follow up evaluation, stratified according to the actual treatment, are shown in the table Deferiprone was less efficacious in controlling both LIC and ferritin levels compared to combination therapy (p=0.016 and 0.031, respectively). Fifteen out of 17 patients treated with DFP showed an increase in LIC, despite using the recommended dose. Six out of 9 patients treated with DFX, most at a low dose, showed an increase in LIC. There were no differences in changes in the cardiac parameters (LVEF, cardiac T2*) in between treatment groups. The efficiency of DFP and DFX, which represents the ratio of iron excreted to the theoretical maximum of iron that could be bound by the chelators, was calculated at 1.8±0.9 % and 15.2 ± 3.6 %, respectively. Conclusions Current iron chelation therapy regimens are able to render iron load-free many patients with thalassemia major. As iron accumulation from transfusions continues, a fine balance needs to be found in which neither worsening of iron overload nor toxicity from excessive dose of iron chelators will occur. This study showed that at low levels of iron overload both combination therapy and DFX can control iron accumulation, whether monotherapy with DFP may be insufficient to achieve iron balance in many patients. The dose of the chelators needs to be adjusted according to the needs and the clinical course of the patients, which can be predicted by the trend of the ferritin levels. Furthermore, it should be kept in mind that at low levels of iron overload, the iron chelators' efficiency may be lower than previously described. Disclosures: Kattamis: NOVARTIS ONCOLOGY: Honoraria, Research Funding, Speakers Bureau; APOPHARMA: Honoraria. Ladis:NOVARTIS ONCOLOGY: Honoraria, Research Funding; APOPHARMA: Honoraria, Research Funding.

A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Sequential Deferipron–Desferrioxamine versus Deferasirox

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5165-5165
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Dell'Amico Maria Chiara ◽  
D'Ascola Domenico Giuseppe ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Mean Difference ◽  
Quantitative Mri ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study

Abstract Abstract 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.

Myocardial Tissue Characterization By Cardiac MR Imaging In Myelodysplastic Syndromes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5211-5211
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giancarlo Carulli ◽  
Esther Natalie Oliva ◽  
Francesco Arcioni ◽  
...  
Keyword(s):  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Myelodysplastic Syndromes ◽  
Tissue Characterization ◽  
Chelation Therapy ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Lv Function ◽  
Myocardial Segment ◽  
Apical Region

Abstract Introduction Magnetic Resonance Imaging (MRI) provides unique insight regarding tissue characterization in the heart. We reported the baseline MRI findings at the end of the recruitment in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study. In particular, we evaluated the distribution of iron overload in the whole left ventricle (LV) and he presence of myocardial fibrosis in patients with myelodysplastic syndromes (MDS); the association with LV function was also investigated. No data are available in the literature about this issue. Methods MIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam. Mean age was 71.7±8.5 years and 17 patients were females. MIO was assessed using a multislice multiecho T2* approach. Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement acquisitions. Results We found 27 (56.3%) patients with no MIO (all 16 segmental T2* values >20 ms). The remaining patients showed an heterogeneous MIO (some segments with T2* values >20 ms and other segments with T2* values <20 ms) and of them 2 (9.5%) showed a global T2* value <20 ms, indicating significant MIO. A reduced LV ejection fraction (EF) was found in the 29.5% of cases and a reduced RV EF in the 23.3%. There was not a significant association between heart T2* values and LV EF. Myocardial fibrosis was detected in the 35.9% of the patients. Three patients showed an ischemic pattern and one of them had a transmural fibrosis in the LV apical region. Out of the 3 patients with an ischemic pattern, only one patient had a positive history for a previous myocardial infarction. The majority of the patients had two or more foci of myocardial fibrosis, involving more frequently the septal segments. Patients with myocardial fibrosis were significantly older (75.4±7.9 vs 68.9±7.6 yrs; P=0.019). Global heart T2* and LV volumes were not significantly different between patients with and without fibrosis. The LV EF was lower in fibrotic patients but the statistical significance was not reached (58.4±11.7 vs 64.8±8.9 %; P=0.067). Conclusions Although a significant heart iron was found only in two cases, nearly half the patients had abnormal T2* values in at least one myocardial segment. This finding underlines the importance to use a multislice approach in order to perform an early diagnosis and prevent a more diffuse iron distribution by chelation therapy. This goal could be critical in patients with myocardial fibrosis that seems to be a relative common findings in the old MDS patients. In fact, an underlying heart damage as represented by fibrosis could make the hearts of the old MDS patients more sensitive to lower levels of accumulated iron. Disclosures: No relevant conflicts of interest to declare.

Long-Term Iron Chelation Therapy with Deferiprone in Patients with Thalassemia Major and Low Iron Load

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3626-3626 ◽  
Author(s):  
Shahina Daar ◽  
Murtadha K. Al-Khabori ◽  
Khalil Al Farsi ◽  
Bader Abdulla Al-Rawahi ◽  
Arwa Z. Al-Riyami
Keyword(s):  
Iron Overload ◽  
Safety Profile ◽  
Chelation Therapy ◽  
Conflicts Of Interest ◽  
Serum Magnesium ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
P Value ◽  
Patient Reported

Abstract Introduction and Objectives: Iron chelators are effective in reducing iron burden and in improving clinical outcomes in patients with transfusional iron overload. However, limited data are available on their efficacy and safety in transfusion-dependent patients with low iron overload, due mainly to concerns of chelation toxicity observed with deferoxamine (DFO) in patients with serum ferritin (SF) < 1500ug/L. Deferiprone (DFP) has markedly lower affinity for iron (pFe3+ log stability constant = 19.9) than that of deferoxamine (26.6), and may provide a better safety profile in patients with low iron overload. The objective of this study is to evaluate the safety and efficacy of DFP in patients with thalassemia major (TM) and SF <500 ug/L. Methods: A total of 32 patients with TM (15 males) who had achieved SF <500 ug/L while on chelation with combined DFO and DFP (n=30) or on deferasirox (DFX) (n=2) had their chelation switched to DFP monotherapy (75-100mg/kg/day). All patients received 50 mg of oral zinc sulfate once a week for the duration of the study. Iron overload was assessed using SF and MRI T2* of liver and heart within 3 months of switch and then 6-12 monthly thereafter. Renal and liver function tests were performed monthly and trace elements (serum magnesium, copper, zinc and selenium) were also assessed. Results: Patients were followed for a median of 4.5 years (Range: 1-11 years). The median age at time of switch was 22.7 years (Range 11-28). The mean packed red blood cell volume transfused during the study was 197 mL/kg/year (Range: 157-282 mL). There was no significant increase in the SF (Baseline 392 ug/L; Last assessment 418 ug/L; p value 0.55) or the liver iron concentration (Baseline 3.44 mg/g dw; Last assessment 3.1 mg/g dw; p value 0.54) during the follow up. On the contrary, there was a statistically significant improvement in the cardiac T2* (Baseline 30 ms; Last assessment 38 ms; p <0.001). DFP was discontinued in 28% of patients (Ineffective in 3; Agranulocytosis in 1; Pregnancy in 1; Bone marrow transplantation in 2; Deaths in 2). The two deaths were unrelated to the chelation therapy (Decompensated HCV related liver cirrhosis and severe hypoglycaemia in a patient with diabetes mellitus). Two patients had mild asymptomatic hypocalcemia, and one had low copper levels. All three patients normalized their results with no treatment and without stopping DFP. No patient reported gastrointestinal disturbances or arthralgia, and none had elevation of liver enzymes or serum creatinine. Conclusion: Long-term DFP therapy in patients with TM and low iron overload was effective in stabilizing SF and LIC and was associated with improvement in the myocardial iron. The safety profile was consistent with those observed during therapy in patients with more severe iron burden and there were no increase in the unexpected adverse drug reactions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Alaa Mutter Jabur Al-Shibany ◽  
AalanHadi AL-Zamili
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Iron Level ◽  
The Mean ◽  
T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

scholarly journals The Effect of Chronic Viral Hepatitis on Serum Ferritin Level in Thalassemia Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4819-4819
Author(s):  
Natthapat Rujeerapaiboon ◽  
Adisak Tantiworawit ◽  
Pokpong Piriyakhuntorn ◽  
Thanawat Rattanathammethee ◽  
Sasinee Hantrakool ◽  
...  
Keyword(s):  
Viral Load ◽  
Iron Overload ◽  
Viral Hepatitis ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Iron Concentration ◽  
Chronic Viral Hepatitis ◽  
The Mean

Background: Serum ferritin is widely used as a marker of iron overload in thalassemia patients. However, the ferritin level is affected by active infections or inflammation. The association between viral hepatitis and serum ferritin level in thalassemia patients is still unclear. This study aimed to determine the effect of chronic viral hepatitis on serum ferritin level in thalassemia patients. Methods: This was a cross-sectional study in thalassemia patients aged ≥15 years-old at Chiang Mai University hospital. We expected that thalassemic patients in our clinic have a mean serum ferritin of 767 ng/mL with a standard deviation of 210 ng/mL. As a result, we have to enroll a total of 28 patients to demonstrate 30% difference of mean serum ferritin when the power was set at 80% with alpha level of 0.05. Information on chronic viral hepatitis, mean serum ferritin and liver iron concentration (LIC) as measured by T2* MRI were collected. Chronic viral hepatitis status was confirmed by either HBV DNA or HCV RNA testing. Patients were categorized to hepatitis and non-hepatitis group. Serum ferritin levels were compared between two groups. LIC measurement was used as a gold standard for iron overload. Subgroup analysis was performed according to iron overload and transfusion requirement status. Categorical and continuous variables were compared using the Chi-squared test and T-test, respectively. The correlation between viral loads and mean serum ferritin levels was analyzed by Pearson's correlation. Result: Of 32 thalassemia patients (25 non-transfusion dependent [NTDT] and 7 transfusion dependents [TDT]), 13 patients had chronic viral hepatitis (7 with hepatitis B and 6 with hepatitis C infections). The LIC between hepatitis and non-hepatitis groups were not significantly different (7.28 [SD 4.7] vs 9.08 [SD 5.2] mg Fe/g, p=0.19). In the higher LIC group (≥ 5 mg Fe/g), the mean serum ferritin level was higher in the hepatitis group than non-hepatitis group (1,776 [SD 488] vs 967 [SD 860] ng/mL, p=0.03). For the lower LIC group (<5 mg Fe/g), the mean ferritin levels were not significantly different between the hepatitis and non-hepatitis groups (646 [SD 224] vs 459 [SD 205] ng/mL, p=0.22). The correlation between the viral load and mean ferritin level in NTDT group showed a significant linear correlation with R=0.7 (p=0.04). Conclusions: We observe a higher serum ferritin level among thalassemia patients who concurrently have chronic viral hepatitis. Chronic viral hepatitis is a possible cause of a falsely high ferritin level in these patient population. Furthermore, the viral load is positively correlated with serum ferritin level. Disclosures No relevant conflicts of interest to declare.

A Multi-Center, Open Label Study Evaluating the Efficacy of Iron Chelation Therapy with Deferasirox in Transfusional Iron Overload Patients with Myelodysplastic Syndromes or Aplastic Anemia Using Quantitative R2 MRI

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3649-3649 ◽  
Author(s):  
Yoo-Hong Min ◽  
Hyeoung Joon Kim ◽  
Kyoo Hyung Lee ◽  
Sung-Soo Yoon ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Transfusion Requirement ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Dry Weight ◽  
Mean Value ◽  
One Year

Abstract Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p<0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient’s transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients.

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