5-Azacytidine is a cytidine analogue that is capable of activating repressed genes in tissue-culture cells and has been shown to increase hemoglobin-F production in anemic baboons. This drug was administered to a patient with severe beta-thalassemia in an attempt to stimulate hemoglobin-F production.
What causes thalassemia?
Thalassemia (thal) is an autosomal recessive, hereditary, chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains (α-thal) or β-globin chains (β-thal) that compose the major adult hemoglobin (α 2β 2). It is caused by one or more mutations in the corresponding genes.
What is oxidative stress in beta thalassemia?
In β-thal, oxidative stress is mainly the consequence of the unstable Hbs (hemichromes) and IO and it mediates many of its symptoms due to oxidative damage to RBCs (anemia), platelets, (hypercoagulable state) and leukocytes (recurrent infections) as well as cells in various vital organs (heart and liver) and the endocrine glands 21.
Is film-coated tablet formulation of deferasirox well tolerated in patients with thalassemia?
: New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study. Am J Hematol.2017;92(5):420–8. 10.1002/ajh.24668 [PMC free article][PubMed] [CrossRef] [Google Scholar]F1000 Recommendation
What is the cause of beta-thalassemia?
Conclusion Beta-thalassemia is caused by mutations in the β-globin gene, resulting in partial or complete deficiency of its product. This deficiency and the accompanying excess of the unmatched α-globin chains result in oxidative stress, dyserythropoiesis, and chronic anemia.
What is the most effective in thalassemias treatment?
Stem cell or bone marrow transplants are the only cure for thalassaemia, but they're not done very often because of the significant risks involved. Stem cells are produced in bone marrow, the spongy tissue found in the centre of some bones, and have the ability to develop into different types of blood cells.
Which therapy is used to treat thalassemia?
Doctors use three standard treatments for moderate and severe forms of thalassemia. These treatments include blood transfusions, iron chelation (ke-LAY-shun) therapy, and folic acid supplements. Other treatments have been developed or are being tested, but they're used much less often.
How is beta thalassemia managed?
Treatment may include: Regular blood transfusions. Medicines to reduce extra iron from your body (called iron chelation therapy) Surgery to remove the spleen, if needed.
What are the current methods for the clinical diagnosis of β-thalassemia?
Thalassemia can be detected and diagnosed via several laboratory examinations such as DNA analysis (genetic testing), complete blood count (CBC), blood smear, prenatal testing (genetic testing of amniotic fluid), iron studies, and hemoglobinopathy (Alqahtani et al., 2018).
How does blood transfusion help thalassemia?
Blood transfusions could be a regular thing if you or your child has a blood disorder called beta thalassemia. The disease causes a drop in the amount of red blood cells you have. A transfusion gives you healthy red blood cells from a donor to make up for the ones you don't have.
How is thalassemia anemia treated?
Many times people with thalassemia are prescribed a supplemental B vitamin, known as folic acid, to help treat anemia. Folic acid can help red blood cells develop. Treatment with folic acid is usually done in addition to other therapies.
Is there any cure for beta thalassemia?
Blood transfusions and chelation do not cure beta thalassemia. Some people with beta thalassemia intermedia and major can be cured with a stem cell transplant.
How is thalassemia treated in adults?
If you have mild thalassemia, you might not need treatment. But more severe forms might require regular blood transfusions. You can take steps to cope with fatigue, such as choosing a healthy diet and exercising regularly.
What is gene therapy in thalassemia?
β-thalassemia gene therapy is based on the transfer of a human β-globin gene into autologous HSCs, which resolves the absence of compatible donors and eliminates the risk of GVHD and graft failure associated with allogeneic BMT.
What treatments are available for thalassemia and its symptoms?
For moderate to severe thalassemia, treatments might include:Frequent blood transfusions. More severe forms of thalassemia often require frequent blood transfusions, possibly every few weeks. ... Chelation therapy. This is treatment to remove excess iron from your blood. ... Stem cell transplant.
Which laboratory investigation is best used for the diagnosis of beta thalassemia major?
Thalassemias and abnormal hemoglobin diagnoses require a combination of laboratory tests including the measurement of red blood cell indices by automatic hematology analyzer, Hb analysis, and quantification of Hb A2 and Hb F.
Which type of Haemoglobin HB is useful in the detection of beta thalassemia carrier?
3. Interpretation of the screening tests. The β-thalassemia carriers always have positive OFT, MCV less than 80 fL, MCH less than 27 pg, and negative HbE.
What are the criteria for thalassemia major?
Criteria. INCLUSION CRITERIA: Thalassemia major with progressive disease or complications of iron overload despite traditional transfusion and iron chelation therapy. Thalassemia major in which standard transfusion therapy or iron chelation therapy is contraindicated.
What is the normal bilirubin level?
Bilirubin greater than1.5X upper limit of normal, unless the abnormal bilirubin can be accounted for by indirect hyperbilirubinemia due to hemolysis or Gilbert's Disease. Serum albumin less than 3g/dl. Creatinine greater than 2mg/dl and creatinine clearance less than 60ml/min.
Does 5-azacytidine increase red cell production?
The purpose of this protocol is to test the hypothesis that induction therapy with 5-azacytidine, followed by maintenance treatment with oral phenylbutyrate will enhance gamma globin synthesis, increase red cell production and partially or substantially correct the anemia in patients with homozygous beta-thalassemia.