Hydroxyurea (hydroxycarbamide) for transfusion-dependent β-thalassaemia

Ansari, Saqib Hussain; Lassi, Zohra S; Khowaja, Salima; Adil, Syed Omair; Shamsi, Tahir

doi:10.1002/14651858.cd012064.pub2

Cited by 22 publications

(24 citation statements)

References 24 publications

(13 reference statements)

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“…These results indicate that MITF can be used as a target gene for melanoma treatment [15,54,55]. HU therapy is used for sickle cell anemia [56], transfusion-dependent β-thalassemia [57], melanoma [34] and other conditions. miRNAs that were differentially expressed under HU treatment are also involved in these treatments [35,36,58].…”

Section: Discussionmentioning

confidence: 86%

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Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p

et al. 2021

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miRNAs are a family of short, noncoding RNAs that are involved in many processes in melanoma cells. MITF acts as a master regulator of melanocyte function, development and survival by modulating various genes. Hydroxyurea (HU) is used to treat melanoma, and miRNA expression is altered after HU treatment in B16 melanoma cells. In this study, we screened for miRNAs that were upregulated after HU treatment and that targeted the MITF gene. We found that miR-7013-3p exhibited increased expression after HU treatment and could bind to MITF. miR-7013-3p inhibited melanin production, proliferation, and migration and promoted apoptosis in B16 melanoma cells. The results may provide more information on the roles of miR-7013-3p in B16 melanoma cells.

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Section: Discussionmentioning

confidence: 86%

“…HU therapy is used for sickle cell anemia 56 , transfusion-dependent β-thalassemia 57 , melanoma 34 and other conditions. miRNAs that were differentially expressed under HU treatment are also involved in these treatments 35 , 36 , 58 .…”

Section: Discussionmentioning

confidence: 99%

Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p

et al. 2021

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“…2 , 32 Indeed, survival of patients with haemoglobin E thalassaemia in other Asian countries, which lack the publicly financed, freely delivered health-care system of Sri Lanka, 33 is likely to be poorer than that reported in this study. Particularly in countries with ongoing blood shortages, controlled clinical trials to evaluate the benefits and risks of different transfusion regimens, in parallel with evaluation of drugs to increase fetal haemoglobin 34 or total haemoglobin, 35 are crucially needed to address these fundamental questions in this under-studied disease.…”

Section: Discussionmentioning

confidence: 99%

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study

Premawardhena

Ediriweera

Sabouhanian

et al. 2022

The Lancet Global Health

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Background Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. MethodsIn this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. Findings 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2•51, 95% CI 1•16-5•43), patients with a history of serious infections (adjusted HR 8•49, 2•90-24•84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1•03, 1•01-1•06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4•5 g/dL (vs concentration >4•5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival.Interpretation Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.

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“…There are currently no oral treatments for β-thalassemia that consistently moderate anemia, while also reducing serum iron levels and TSAT. Hydroxyurea is orally administered and has been used for many years as an inducer of fetal hemoglobin, but results are inconsistent and most of the evidence supporting its use is retrospective or of low quality [24,[62][63][64][65][66][67][68][69][70][71]. Controlled trials are required to examine whether there is a consistent response to hydroxyurea, irrespective of differences in thalassemia genotype, previous transfusion history, and treatment policies in different regions.…”

Section: Expert Opinionmentioning

confidence: 99%

Oral ferroportin inhibitor vamifeport for improving iron homeostasis and erythropoiesis in β-thalassemia: current evidence and future clinical development

Porter

Taher

Viprakasit

et al. 2021

Expert Review of Hematology

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Introduction: In β-thalassemia, imbalanced globin synthesis causes reduced red blood cell survival and ineffective erythropoiesis. Suppressed hepcidin levels increase ferroportin-mediated iron transport in enterocytes, causing increased iron absorption and potentially iron overload. Low hepcidin also stimulates ferroportin-mediated iron release from macrophages, increasing transferrin saturation (TSAT), potentially forming non-transferrin-bound iron, which can be toxic. Modulating the hepcidinferroportin axis is an attractive strategy to improve ineffective erythropoiesis and limit the potential tissue damage resulting from iron overload. There are no oral β-thalassemia treatments that consistently ameliorate anemia and prevent iron overload. Areas covered: The preclinical and clinical development of vamifeport (VIT-2763), a novel ferroportin inhibitor, was reviewed. PubMed, EMBASE and ClinicalTrials.gov were searched using the search term 'VIT-2763ʹ. Expert opinion: Vamifeport is the first oral ferroportin inhibitor in clinical development. In healthy volunteers, vamifeport had comparable safety to placebo, was well tolerated and rapidly decreased iron levels and reduced TSAT, consistent with observations in preclinical models. Data from ongoing/ planned Phase II studies are critical to define its potential in β-thalassemia and other conditions associated with iron overabsorption and/or ineffective erythropoiesis. If vamifeport potentially increases hemoglobin and reduces iron-related parameters, it could be a suitable treatment for non-transfusiondependent and transfusion-dependent β-thalassemia.

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Hydroxyurea (hydroxycarbamide) for transfusion-dependent β-thalassaemia

Cited by 22 publications

References 24 publications

Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p

Hydroxyurea regulates the development and survival of B16 Melanoma Cells by upregulating MiR-7013-3p

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study

Oral ferroportin inhibitor vamifeport for improving iron homeostasis and erythropoiesis in β-thalassemia: current evidence and future clinical development

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