Living with Transfusion-Dependent β-Thalassaemia (TDT)

In its most severe form and without adequate care, thalassaemia can be lethal in early childhood, and although Annual International Thalassaemia Day has come and gone, awareness is paramount.

Andrew Obenshain, Head of Europe at gene therapy company bluebird bio, looks into what it means to live with thalassaemia, with a particularly focus one of the most severe forms – Transfusion-Dependent β-Thalassaemia.

Wednesday 8 May 2019 marked the annual International Thalassaemia Day. This is a distinguished day for the global thalassaemia community to not only raise awareness of the disease among the public, but also to honour all thalassaemia patients fighting for their right to a better quality of life. It is also an opportunity to remember those thalassaemia patients who have lost their lives to the disease.

What do you know about Thalassaemia?

Thalassaemia is a somewhat unknown condition and there are many different types. It is a shocking moment for parents when they discover that their child is suffering from it. As an inherited genetic condition, thalassaemia is part of a group of blood disorders known as Haemoglobin disorders. This means that they affect the haemoglobin in the blood, which is an important substance or protein found in the red blood cells. Essentially, thalassaemia reduces the ability of the blood cells to provide the body with oxygen.

In its most severe form and without adequate care, thalassaemia can be lethal in early childhood. Children are born with the condition if their parents are carriers of it. These parents may be healthy and unaware of their status or diagnosed as slightly anaemic depending on which type of thalassaemia they have. In Italy for example, there are an estimated 3 million healthy carriers¹.

The rare genetic disease of TDT

An acute form of thalassaemia is transfusion-dependent β-thalassaemia (TDT), also known as β-thalassaemia major, characterised by severe anaemia. 1.5% of the global population are β-thalassaemia carriers² and 60,000 symptomatic individuals are born annually³. Although it is a rare genetic disease, it is more prevalent in the Mediterranean area and particularly in Italy, where it is estimated that there are over 6,500 cases⁴.

A diagnosis is usually made during the first two years of life. Patients with TDT have impaired production of the β-globin chain, so they either have a reduction or a complete absence of the ß-globin protein⁵.

This means that they are not able to make enough haemoglobin to survive, so they lack functional red blood cells, leadings to a deficiency of oxygen. That’s why they need regular blood transfusions, some as often as every two to four weeks. In Germany for example, 678 patients received at least one blood transfusion in 2015, and 28.1% of these people required eight or more transfusions every year⁶.

The lifelong dependence of red blood cell transfusions

Because of their oxygen deficiency, patients with TDT suffer from chronic anaemia, serious health problems and reduced life expectancy⁷. Their lifelong dependence on red blood cell transfusions also means that they experience numerous side effects and complications including iron overload. These may cause organ damage, diseases of the musculoskeletal system, the respiratory system, metabolic diseases and reduced survival compared to the general population^8,9,10,11.

It’s therefore no coincidence that 82% of 131 people interviewed in a recent Italian national patient survey for International Thalassaemia Day stated that the disease has a significant impact on their daily lives¹².

The survey showed that 42% of respondents spent more than 30 days in hospital in 2018 for transfusions and medical check-ups, and in addition had to fulfil all the other obligations related to the management of the disease like administrative requirements¹³. This time was directly taken away from family time, relationships, sports, leisure and holidays and of course education or work.

Significant advancement made

Of course, progress is being made. The standard of care for TDT patients has advanced significantly and survival in thalassaemia has dramatically improved over the last twenty years.¹⁴ However, the impact of living with the condition should not be underestimated. Mortality remains increased, at 13.5% in 2008 compared to the general population¹⁴.

Leading a ‘normal’ life is an often-expressed priority for those affected, and we should look to possible innovation in the future of treatment for these patients. Additional endeavours to address the quality of life of TDT patients are essential to improve the outcomes of this rare condition.

TDT is a severe, progressive, genetic disease that impacts patients for life^14,15. International Thalassaemia Day is an opportunity to increase public awareness on the very tangible and ever-present effect that living with TDT has on day-to-day lives.

The theme for 2019’s International Thalassaemia Day is ‘Universal access to quality thalassaemia healthcare services: Building bridges with and for patients’, so let us take this opportunity to increase our understanding of the current and future challenges faced by the thalassaemia community.

We need to appreciate that future treatments demand improved access to high quality, safe and effective healthcare service choices that need to take advantage of the full spectrum of innovation that medical science has to offer, so people can enjoy an even better quality of life.

References

1. 2018 SITE (Italian Society Hemoglobinopathies) National Congress
2. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010; 5: 11.
3. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11.
4. 2018 ASH (American Society of Hematology) Annual Meeting
5. GeneticsHomeReference/p1/para3Ðalanello 2010/p2/col1/para1ÐIF Guidelines 2014/p15/para2
6. Based on a claims database analysis. N=32 patients with at least one blood transfusion were identified in the InGef database and extrapolated to the German population, resulting in 678 overall ß-thalassemia patients with at least one blood transfusion
7. Baldini 2012/p1/para2ÐIF Guidelines/p43/para1Ð_
8. Bonifazi 2017/p4/para2; para3Ðubman 2015/p2/para5;p3/para2-3;p4/para4
9. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 3rd ed. Thalassaemia International Federation. 2014. ISBN-13:978-9963-717-06-4.
10. Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry 2000–2010. Bone Marrow Transplant. 2016;51(4):536-541.
11. Ladis V, Chouliaras G, Berdoukas V, et al. Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population. Eur J Haematol. 2011;86(4):332-8.
12. United Onlus and bluebird bio. (2019) The impact Transfusion-Dependent β-Thalassaemia (TDT) has on the lives of patients and their families.
13. United Onlus and bluebird bio. (2019) The impact Transfusion-Dependent β-Thalassaemia (TDT) has on the lives of patients and their families.
14. Eur J Haematol. 2011 Apr;86(4):332-8. doi: 10.1111/j.1600-0609.2011.01582.x.
15. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 3rd ed. Thalassaemia International Federation. 2014. ISBN-13:978-9963-717-06-4.
16. Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry 2000–2010. Bone Marrow Transplant. 2016;51(4):536-541.

Andrew Obenshain
bluebird bio
www.bluebirdbio.com