Role of deferiprone in chelation therapy for transfusional iron overload

Hoffbrand, A. V.; Cohen, Alan R.; Hershko, C

doi:10.1182/blood-2002-06-1867

Cited by 228 publications

(179 citation statements)

References 72 publications

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“…The incidence of fluctuation of hepatic transaminase levels after deferiprone exposure found in our Thai patients seemed to be higher than Caucasian population [21,42,54] but somewhat similar to Chinese patients [41,59]. Around 50% of the incidences were mild and transient; patients could continue on the study drug without interruption.…”

Section: Discussionsupporting

confidence: 57%

“…In addition, patients could be safely prevented from future cardiac and hepatic problems at this SF level. To achieve this goal, it might be sensible to increase the dose of deferiprone up to 100 mg/kg/day [53,54] or combine deferiprone with 3-4 days a week of desferoxamine (40-60 mg kg 21 ) [55] in patients who are nonresponse patients after 6-month evaluation of deferiprone monotherapy or in patients who subsequently lose their primary response to deferiprone when their iron load status have declined from the start but remain higher than needed normalized levels [56]. However, this approach must be treated with caution under a rigorous assessment since experience with deferoxamine has suggested that lowering iron chelator doses should be used when iron levels are low to minimize drug toxicity [6].…”

Section: Discussionmentioning

confidence: 99%

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Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

et al. 2013

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Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy-three pediatric patients with severe b thalassemias, age range 3.2-19 years, were recruited to a 1-year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty-four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.164.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml 21 . Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml 21 had the most significant fall of SF at 1 year. A subgroup analysis by MRI-T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug-related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251-260,

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

et al. 2013

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“…The first oral iron chelator deferiprone (Ferriprox®), introduced already 20 years ago, did not fulfill the expectations. The license of the drug remained limited to second-line therapy of patients with thalassemia major, bearing the risk of neutropenia and agranulocytosis in a frequency of about 0.5-1% [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

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International audienceBlood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade®) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53–91) were enrolled. Deferasirox administered in a once-daily dose of 20–30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 µg/L (range 665–6,900) to 413 µg/L (range 105–3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 µmol/g ( = 0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine β2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow

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“…As one unit of blood contains between 100 and 250 mg of iron [3,18] transfusiondependent patients with MDS invariably develop iron overload at a rate of approximately 0.5mg per kg of body weight per day [19] and typically after 10-20 transfusions [2,20]. The circulating non-transferrin-bound iron produces hydroxyl and oxygen radicals that cause lipid peroxidation and damage to cell membranes, protein, and DNA [2,21], especially in target organs such as heart, liver, and endocrine glands [1,22].…”

Section: Introductionmentioning

confidence: 99%

“…Two iron chelating agents are approved worldwide, parenteral deferoxamine (Desferal®, Novartis) and oral deferasirox (Exjade®, Novartis). A third oral agent, deferiprone (Ferriprox®, Apopharma) is approved in some Asian and European countries, but not in the USA and Canada due to safety concerns [19,29,30,31].…”

Section: Introductionmentioning

confidence: 99%

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

et al. 2011

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACT Transfusion-dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions.Transfusion-dependency is associated with leukemic progression and shorter survival.Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76 and median age at diagnosis of MDS was 74. Patients had received an average of 13.4+7.6 RBC units in the past four months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1550g/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of IPSS, FAB, and/or WHO status, though chelated patients had received more RBC transfusions (p=0.014).Iron chelation therapy may be underutilized in transfusion-dependent patients.

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Role of deferiprone in chelation therapy for transfusional iron overload

Cited by 228 publications

References 72 publications

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

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Role of deferiprone in chelation therapy for transfusional iron overload

Cited by 228 publications

References 72 publications

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

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Product

Resources

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Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand