Review question
We reviewed whether different types of stem cell transplantation are safe and effective in people with transfusion-dependent β-thalassaemia.
Background
Thalassaemia is a disorder that occurs because of a mutation in either the α- or β-globin genes causing decreased production of haemoglobin (a protein found in red blood cells that carries oxygen) and increased destruction of red blood cells. Decreased production of haemoglobin and destruction of red blood cells leads to anaemia and significant morbidity in affected individuals. While anaemia can be treated effectively with regular blood transfusions, repeated transfusions lead to the accumulation of iron in the body, which unless treated with iron chelation can result in multiorgan disease particularly heart and lung. These toxicities tend to accumulate over time leading to reduced quality of life and early death. Additionally, blood transfusions do not provide a cure. The use of hematopoietic (blood-forming) stem cell transplantation involves replacing the unhealthy hematopoietic stem cells with normal hematopoietic stem cells from either a healthy donor (allogeneic hematopoietic stem cell transplantation) or genetically correcting the recipient's own cells and reinfusing them back into the individual (autologous gene therapy). These stem cells then produce normal red blood cells containing normal amounts of globin chains and thus ameliorate anaemia.
Search date
The evidence is current to: 07 April 2021.
Key results
The review authors did not find any randomised controlled trials assessing the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia.
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.
To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.
Date of the most recent search: 07 April 2021.
Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review.
No relevant trials were retrieved after a comprehensive search of the literature.