The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review

Ballas, Samir K.; Zeidan, Amer M.; Duong, Vu H.; DeVeaux, Michelle; Heeney, Matthew M.

doi:10.1002/ajh.25103

Cited by 52 publications

(31 citation statements)

References 29 publications

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“…All three diseases also give rise to hemolytic anemia resulting in symptoms of fatigue [ 17 ] and shortness of breath [ 18 ], sleep disturbances [ 19 , 20 ], and jaundice [ 16 , 17 ]. As a result of blood transfusions used as a treatment in these three diseases, iron overload occurs, resulting in heart [ 21 , 22 ] or liver disease [ 22 , 23 ], infections [ 16 ], and osteoporosis [ 24 , 25 ]. Leg ulcers are another complication of all three diseases [ 16 , 21 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency

Salek

Ionova²,

Johns³

et al. 2018

Qual Life Res

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Purpose Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient’s quality of life. With new therapies, reliable, valid, and relevant patient-reported outcome (PRO) tools are required for use in clinical trials. Methods Systematic literature search identified no current PRO tools for capturing/measuring the impact of PKD and treatments in clinical trials. Therefore, the search strategy was revised to consider conditions analogous to PKD in terms of symptoms and impacts that might serve as parallels to the experience in PKD; this included sickle cell anemia, thalassemia, and hemolytic anemia. Psychometric properties, strengths, and weakness of selected appropriate PRO instruments were compared, and recommendations made for choice of PRO tools. Results In adult populations, EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, covering generic HRQoL, and core symptoms such as fatigue. In pediatric populations, PedsQL Generic Core Scale to measure HRQoL and PedsQL MFS scale to measure fatigue are recommended. Conclusions Some symptoms/life impacts may be unique to PKD and not observable in analogous conditions. A ‘Physico-Psychosocial Model’ derived from the ‘Medical Model’ is proposed to form the basis for a hypothesized conceptual framework to address the development of PKD-specific PRO instruments. Electronic supplementary material The online version of this article (10.1007/s11136-018-2025-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency

Salek

Ionova²,

Johns³

et al. 2018

Qual Life Res

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“…Successful experiences support the use of iron chelation therapy for the treatment of systemic diseases with an iron accumulation component, such as thalassemia major, sickle cell disease and cardiomyopathy associated with hereditary hemochromatosis [59,60,61,62,63,64,65,66,67]. The chelators used in these therapies are deferoxamine, deferasirox, deferiprone and PBT2.…”

Section: Clinical Trials Using Iron Chelationmentioning

confidence: 99%

New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases

2018

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Iron chelation has been introduced as a new therapeutic concept for the treatment of neurodegenerative diseases with features of iron overload. At difference with iron chelators used in systemic diseases, effective chelators for the treatment of neurodegenerative diseases must cross the blood–brain barrier. Given the promissory but still inconclusive results obtained in clinical trials of iron chelation therapy, it is reasonable to postulate that new compounds with properties that extend beyond chelation should significantly improve these results. Desirable properties of a new generation of chelators include mitochondrial destination, the center of iron-reactive oxygen species interaction, and the ability to quench free radicals produced by the Fenton reaction. In addition, these chelators should have moderate iron binding affinity, sufficient to chelate excessive increments of the labile iron pool, estimated in the micromolar range, but not high enough to disrupt physiological iron homeostasis. Moreover, candidate chelators should have selectivity for the targeted neuronal type, to lessen unwanted secondary effects during long-term treatment. Here, on the basis of a number of clinical trials, we discuss critically the current situation of iron chelation therapy for the treatment of neurodegenerative diseases with an iron accumulation component. The list includes Parkinson’s disease, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, Huntington disease and Alzheimer’s disease. We also review the upsurge of new multifunctional iron chelators that in the future may replace the conventional types as therapeutic agents for the treatment of neurodegenerative diseases.

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“…Once-daily oral administration of deferasirox dispersible tablet (DT) formulation presented a better option, with greater compliance and quality of life over parenteral deferoxamine [ 9 ]. Currently, there are no direct comparison studies for the 2 oral chelators; however, once-daily simpler use of deferasirox has been projected to be a more cost-effective option than the thrice-daily administration of oral deferiprone in the management of long-term complications [ 7 , 10 ]. The deferasirox film-coated tablet (FCT) formulation, with a simpler oral administration and improved palatability and gastrointestinal (GI) tolerability compared with deferasirox DT, offers a better option for optimal patient acceptance and improved compliance to long-term therapy [ 1 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study

et al. 2020

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Background: Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks. Methods: The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study. Results: Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (~ 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (> 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of ~ 90% and persistence (continuous use for ≥ 30 days) of > 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%).

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The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review

Cited by 52 publications

References 29 publications

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency

New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases

Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study

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