Paediatric Haematology, Oncology and Stem Cell Transplantation
Sickle cell disease and thalassaemia
Sickle cell disease and thalassaemia belong to the group of what are referred to as haemoglobinopathies. With seven per cent of the world's population affected, they are the most common monogenic hereditary diseases worldwide.
Their incidence has increased significantly in Germany in recent years. Quality of life is severely impaired in severe forms of haemoglobinopathies, and life expectancy is significantly shorter than in the normal population.
Treatment
The only curative treatment is stem cell transplantation and, in future, gene therapy. The treatment of haemoglobinopathies is a multidisciplinary challenge and should only be carried out in specially qualified centres.
Our department is a national reference centre and an internationally renowned centre for the treatment of haemoglobinopathies, offering a comprehensive programme for the diagnosis and treatment of these diseases. We can offer a high probability of different options for curing these diseases, particularly to children and adults who do not have a suitable sibling donor.
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Thalassaemia is a disorder in which haemoglobin is produced in insufficient quantities or not at all.
This shortens the lifespan of erythrocytes and increases ineffective blood formation.
Dependence on transfusions
Patients with severe forms of thalassaemia are ‘transfusion-dependent’ for life. Transfusion dependency and ineffective blood formation lead to a steadily increasing iron overload in the body, which cannot be adequately treated with chelation therapy. The iron deposits cause tissue damage to the liver, hormone-producing organs and the heart.
This irreversible damage is a major problem in transfusion-dependent thalassaemia, which leads to a significant reduction in life expectancy despite optimum treatment with medication.
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With sickle cell disease, haemoglobin is altered in such a way that the erythrocytes deform into a sickle shape in oxygen-deficient tissue.
The deformed erythrocytes in severe forms of sickle cell disease block the blood vessels and trigger an inflammatory process in the vessel walls, causing the typical and sometimes life-threatening sickle cell crises that sickle cell patients suffer from so much:
- Pain-related crises
- Bone infarcts
- Splenic sequestration crises
- Acute chest syndrome
- Stroke, etc.
Sickle cell vasculopathy
The main long-term problem is sickle cell vasculopathy: the chronic damage to blood vessels caused by recurrent inflammation leads to heart, lung and kidney failure, which is difficult or impossible to treat with medication. The life expectancy of these patients is significantly reduced despite optimum medication.
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- Counselling and diagnosis in cases of positive newborn screening for sickle cell disease and newly diagnosed haemoglobinopathies
- Execution of a programme of transfusions for haemoglobinopathies requiring a transfusion, accompanied by the necessary chelation therapy (iron-binding medication)
- Screening tests for the early detection of organ damage:
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- Laboratory tests
- Determination of liver and heart iron
- Neurocognitive tests
- Measurement of pulmonary function
- Transcranial Doppler and MRI examinations to determine the integrity of the cerebral vessels
- MRI examinations to determine existing bone infarcts
- Interdisciplinary management of complications of sickle cell disease and iron overload
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Stem cell transplantation and, in future, gene therapy are the only generally available curative therapies for all haemoglobinopathies. A distinction is made between:
- Allogeneic stem cell transplantation: bone marrow or peripheral stem cells from a suitable family donor or, in rare cases, from an unrelated donor are transplanted.
- Haploidentical stem cell transplantation: this is a special form of allogeneic transplantation. Donors and recipients only need to be partially compatible in terms of HLA characteristics. In these cases, the donor is a parent, sibling or, in special cases, another close relative (cousin), meaning that almost every patient can be offered a stem cell transplant. An international study evaluating the significance of haploidentical stem cell transplantation is headed by our centre (EudraCT number: 2018-002652-33).
- Gene therapy (CRISPR/CAS9 therapy): this method involves modifying the patient's own stem cells so that they once again produce foetal haemoglobin, which is not affected by any of the most common genetic defects.
