Characteristics
Chronic myeloid leukemia (CML) develops in the bone marrow as a result of a genetic rearrangement in the DNA of myeloid cells, a specific type of blood stem cells that gives rise to different types of white blood cells (e.g., neutrophils and monocytes), red blood cells or platelets. The specific genetic aberration that lies at the basis of CML is a translocation between chromosomes 9 and 22, meaning that a section of chromosome 9 switches places with a section of chromosome 22. This creates an extra-short chromosome 22 (the ‘Philadelphia chromosome’) and an extra-long chromosome 9. As a result of this rearrangement, a gene from chromosome 9 is fused to a gene on chromosome 22 to create a new gene called ‘BCR-ABL’. This ‘fusion gene’ gives rise to an abnormal protein on the cell surface of CML cells allowing them to grow out of control. Over time, leukemic cells build up in the bone marrow and spill over into the blood.
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CML is a rare cancer, with about 180 new cases in Belgium in 2021. It can occur at any age, but mainly affects older people. It is also more common in men than and women. Apart from an older age and being male, little is known about the risk factors for the development of CML, although a relation has been identified between CML and the exposure to radiation.
As indicated by the term ‘chronic’, CML tends to progress slowly, and the disease can remain asymptomatic for many years. Over time, however, an excessive number of leukemic cells can crowd the bone marrow and interfere with normal blood cell production. CML is divided into 3 different phases: chronic phase, accelerated phase and blast crisis. Of note, an evolution to these more advanced disease stages is rare and only occurs in patients with a treatment failure.
Symptoms
In the beginning, CML does not cause any signs or symptoms and, as a result, the disease is often diagnosed during a routine blood test. However, when the normal blood cell production gets disturbed, patients will eventually develop symptoms. These symptoms include a general feeling of weakness or fatigue and a tendency to easily pick up infections (leading to fever). In addition to this, CML can be associated with night sweats, unexplained weight loss, bone pain and a sense of fullness below the ribs as a result of an enlarged spleen.
Diagnostic tests
The most common sign of CML is an abnormal white blood cell count, which is often found during blood tests for an unrelated health problem or during a routine checkup. Most people with CML have an increased amount of white blood cells with many immature cells called myeloblasts or promyelocytes. Apart from the number of cells, doctors will study the size and shape of the cells and assess whether they contain granules (small spots seen in some types of white blood cells).
While these signs can be suggestive for CML, the diagnosis needs to be confirmed by genetic testing and the identification of a translocation t(9;22). A bone marrow biopsy is not essential, but can be performed, mainly to exclude additional genetic aberrations.
Usually, leukemia does not form tumors and, as a result, medical imaging tests (X-ray, CT-scans, MRI, ultrasound) are not very important in the diagnostic work-up of CML. However, when the disease is suspected to have spread beyond the blood and bone marrow, imaging tests can be requested.
Treatments
The treatment for patients with CML mainly consists of targeted therapy. In fact, following the discovery of the Philadelphia chromosome, tyrosine kinase inhibitors (TKIs) have been developed that specifically block the function of the BCR:ABL fusion protein (e.g., imatinib, dasatinib, nilotinib, bosutinib, ponatinib). With these TKIs, the majority of patients with CML can obtain remission, meaning that the leukemic cells in the blood or bone marrow are completely eradicated, or at least reduced to very low numbers.
An essential part of the management for patients with CML consists of response monitoring. To this end, the BCR-ABl level in the blood is checked every 3 (or 6) months. If the results of this analysis show that the treatment is working well, the therapy is continued without a change. However, when the results show that the therapy isn’t working well, or when the patient is not tolerating the treatment very well, a switch to another TKI can be considered. In about half of the patients, the current TKIs can induce a sustained, deep remission (MR 4.5) after which the treatment can be considered in certain patients. However, also for these patients, there remains a risk for a late relapse and patients need to be followed up for the rest of their life.
For a proportion of CML patients with more advanced disease (accelerated of blast phase), high-dose chemotherapy followed by a stem cell transplantation may be an option. This is especially the case for younger patients who have a donor with a matching tissue type.
Relevant patient organisations
Get connected to different patient organisations that connect you to people with the same medical history. Support amongst peers helps the burden and stress of the daily challenges that come with disorders.
Find below some organisations we can recommend.
Be aware that these groups operate mainly in Dutch or French given their local nature, don’t hesitate to contact them nevertheless.
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