Acute leukaemias are malignant diseases of the haematopoietic system which are characterised by the uncontrolled proliferation of immature precursor blood cells, known as blasts, in the bone marrow. Depending on the type of blood cells affected, a distinction is made between acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL).

Acute leukaemias are rarer than so-called solid tumours such as malignant lung or intestinal tumours. In Germany, four out of every 100,000 adults are diagnosed with acute leukaemia every year. The risk of developing acute leukaemia increases with age; the average age of onset is over 60. In adults, around 80% of acute leukaemias belong to the AML group and around 20% to the ALL group. ALLL is the most common form of leukaemia in children.

The causes of the development of acute leukaemia are only partially understood. However, there are a number of factors that increase the risk of developing the disease. These include damage to the bone marrow caused by radioactive radiation and certain chemicals such as benzene. In addition, chemotherapy and/or radiotherapy for another malignant disease and long-term use of medication that suppresses the immune system are also associated with an increased risk of developing the disease. Very rarely, the development of acute leukaemia is due to hereditary diseases that are associated with an increased risk of leukaemia. These include Down's syndrome, for example. In addition, there are several blood disorders, such as myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPN), which can develop into AML. This is then referred to as secondary AML.

The symptoms of acute leukaemia are usually directly attributable to infiltration of the bone marrow by the leukaemia cells and the resulting suppression of normal haematopoiesis. Typical symptoms are fatigue, pallor, shortness of breath (due to a reduction in red blood cells), infections (due to a reduction in normal white blood cells) and bleeding events (due to a reduction in platelets). Infiltration of other organs and tissues such as the liver, spleen, lymph nodes, bones, gums, skin and central nervous system can result in various symptoms and findings (enlargement of the liver, spleen or lymph nodes, bone pain, swelling of the gums, etc.). Very high leukaemia cell counts in the blood can lead to visual disturbances and other central nervous system deficits as well as bleeding events.

If a tumour is suspected, the attending physician will carry out several examinations in addition to a detailed discussion.

The most important examinations for the detection of acute leukaemia include a medical history and physical examination, laboratory tests and a bone marrow examination.

To assess the function of the most important organs and to recognise concomitant diseases and complications, an X-ray examination and, if necessary, a computer tomography of the chest organs, an ultrasound examination of the abdominal organs, a lung function test, an ECG examination and an ultrasound examination of the heart are required. If the leukaemia has spread outside the bone marrow or peripheral blood, this will be examined histologically in the same way as the bone marrow.

In order to assess the prognosis of an individual patient and determine the most suitable therapy, each acute leukaemia must be described as precisely as possible. Various classification systems of the World Health Organisation, the so-called WHO classification, or the so-called "European LeukamiaNet (ELN) are available for this purpose. These systems take into account changes in the genetic material of the leukaemia cells, the microscopic appearance and certain staining properties of the leukaemia cells, the detection of certain protein molecules on the surface of the leukaemia cells. Furthermore, the patient's medical history, in particular whether the leukaemia has arisen from another blood disease or has developed following chemotherapy and/or radiotherapy for another malignant disease, is relevant for these classifications. In recent years, a large number of outstanding research findings have led to profound insights that have an influence on prognosis assessment and ultimately also therapy.

The choice of treatment for acute leukaemia depends on the exact diagnosis (AML or ALL), the additional characteristics of the leukaemia cells (see above), the age of the patient, their general condition and any concomitant diseases. The following forms of treatment can be considered: curative therapy, palliative therapy, experimental therapy, supportive therapy, observation.

Curative therapy

This form of treatment aims to cure the patient. The most important component of curative therapy is intensive chemotherapy with several different drugs (so-called cytostatics). Such chemotherapy can usually only be carried out in hospital and requires the patient to be in good general health and to have no serious concomitant illnesses. Almost all patients with acute leukaemia who are treated with the aim of a cure are treated within the framework of so-called controlled therapy studies. These serve the purpose of further improving the current standard therapy by comparing different drugs or therapeutic approaches. Numerous studies have shown that patients who are treated in such trials have the best therapy results. Another option for the treatment of acute leukaemia is stem cell transplantation. In this form of therapy, the patient also receives intensive chemotherapy with several different drugs as well as radiotherapy with the aim of killing the leukaemia cells. Healthy stem cells from a suitable donor are then transferred by transfusion.

Palliative therapy

This form of treatment aims to maintain the patient's quality of life. The most important component of palliative therapy is less intensive chemotherapy with drugs that are as well tolerated as possible. The aim is to control the disease by reducing the leukaemia cells in the bone marrow and blood. Palliative therapy is often used for older patients in a reduced general condition or with serious concomitant illnesses. From the point of view of the patient's quality of life, palliative therapy should be carried out under outpatient conditions wherever possible.

Experimental therapy

This involves the use of novel drugs or therapeutic procedures that may be effective in treating acute leukaemia, but whose definitive role in the treatment of these diseases has not yet been conclusively clarified. At Ulm University Hospital, a large number of new experimental therapies are being carried out as part of clinical trials for acute leukaemias. The current status can be seen on our clinic website.

Supportive therapy

This form of treatment does not specifically target the leukaemia, but provides supportive therapy based on the patient's symptoms. The most important supportive measures include the transfusion of red blood cells for anaemia, the transfusion of platelets for bleeding, the administration of antibiotics for infections and the administration of painkillers.

Observation

In some patients who cannot be treated intensively with the aim of a cure, leukaemia progresses very slowly without any serious symptoms. In such cases, a wait-and-see approach with regular check-ups (general condition and blood values) may be sufficient. As the disease progresses, palliative therapy or the initiation of supportive measures is often necessary.

A relapse is the recurrence of acute leukaemia after curative therapy has achieved a complete regression of all signs of the disease. The procedure in the event of a relapse (renewed curative therapy, palliative therapy, experimental therapy, supportive therapy, observation) depends on the specific characteristics of the leukaemia, the patient's age, general condition, any concomitant diseases and the patient's wishes and is determined on a case-by-case basis.

Research is currently being carried out in particular into the development of new types of drugs that enable targeted therapy of acute leukaemia while sparing unaffected organs and tissue. Some of these drugs are already available as part of experimental therapy protocols (see above); their final status in the treatment of acute leukaemia cannot yet be conclusively assessed.