Characteristics
Chronic lymphocytic leukemia (CLL) develops in the bone marrow as a result of mutations in the DNA of lymphoid cells, a specific type of precursor B-cells that gives rise to lymphocytes. In case of CLL, the affected cells are called B-lymphocytes. In normal circumstances, these B-lymphocytes produce antibodies that target viruses, bacteria, cancer cells, and other foreign intruders.
CLL typically affects older people, with the majority of diagnoses in people above the age of 65. It is the most common type of leukemia among adults, with an incidence of 722 cases in Belgium in 2021. CLL usually develops slowly and progresses at a very slow pace. In fact, for many people with CLL, the disease remains asymptomatic and stable for many years, without an impact on their lifestyle or general health. Over time, however, an excessive amount of leukemic cells can crowd the bone marrow and interfere with normal blood cell production.
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Apart from CLL, there are a couple of rare leukemia types with similar features.
Prolymphocytic leukemia (PLL) is characterized by the development of prolymphocytes, an immature form of B- or T-lymphocytes that look very much like normal cells. PLL is similar to CLL but affects a less mature cell type. While CLL usually grows very slowly, B-PLL and T-PLL tend to grow and spread faster. PLL may develop in patients who already have CLL and in this case the disease tends to be more aggressive. However, PLL can also occur in people who have never had CLL.
Hairy cell leukemia (HCL) is a rare, indolent type of leukemia that also develops from B-lymphocytes. However, the leukemic cells in HCL look different from B-CLL cells as they carry extensions on their cell surface which gives them a ‘hairy’ appearance. In addition to this, patients with HCL experience different symptoms than CLL patients and also the treatment of both leukemia subtypes differs. In fact, patients with HCL can experience bleeding symptoms or recurrent infections and their treatment often consists of a combination of cladribine chemotherapy with or without rituximab.
Monoclonal B-cell lymphocytosis (MBL) MBL is not a disease, but rather a condition characterized by an increased number of identical B-cells, often with a CLL signature. Similar to CLL, it is characterized by a high number of abnormal B-cells in the blood (although not so high as in CLL patients). Given the fact that a person with MBL maintains a sufficient number of healthy B-cells, this condition usually remains asymptomatic and generally does not require treatment. However, as MBL increases the risk for the development of CLL, regular blood testing is warranted.
Symptoms
In the beginning, CLL 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, some patients will eventually develop symptoms. This includes a general feeling of weakness or fatigue, regular infections (leading to fever), and the development of a painless swelling of lymph nodes in the neck, underarm, stomach, or groin. In addition to this, CLL can be associated with night sweats, unexplained weight loss, and a tendency for bruising or bleeding. CLL can also lead to an enlarged spleen, resulting in pain and a sense of fullness below the ribs (the latter is often referred to as ‘early satiety’).
Diagnostic tests
CLL is often diagnosed during a routine blood test, revealing a higher-than-normal white blood cell count. To assess whether this higher white blood cell count is caused by CLL, and not by other blood disorders or an infection, a flow cytometry test is performed. Apart from confirming the CLL, flow cytometry can help physicians to characterize the specific leukemia cells, which in turn gives information on the aggressiveness of the disease. Other tests that may be helpful for the diagnosis of CLL include a bone marrow biopsy and an ultrasound of the liver and/or spleen.
To further characterize the disease, doctors will perform genetic tests on blood or bone marrow cells to assess the presence of certain gene mutations, or rearrangements. Apart from giving extra prognostic information, the presence of certain genetic abnormalities also helps to determine the best treatment strategy.
Usually, leukemia does not form tumors and, as a result, medical imaging tests (X-ray, CT-scans, MRI, ultrasound) are less important in the diagnostic work-up of CLL than for solid tumors. However, for some patients where the CLL is suspected to have spread beyond the blood and bone marrow, imaging tests can be requested.
Treatments
Most people with CLL don’t have any symptoms at the time of their diagnosis and do not require any treatment, apart from regular check-ups with their doctor to monitor their health (i.e., watchful waiting). For most symptomatic patients, however, treatment will be initiated.
For the moment, CLL remains to be incurable and the main objective of the treatment is to get the CLL under control (remission). Historically, chemotherapy was the most common treatment for patients with CLL. In recent years, however, targeted therapies have largely replaced chemotherapy as the preferred initial treatment for patients with CLL in need of therapy.
The targeted therapies used in CLL can largely be subdivided into three categories. First of all, Bruton tyrosine kinase inhibitors (e.g., ibrutinib, zanubrutinib or acalabrutinib) specifically block enzymes (tyrosine kinases) that cause blood stem cells to produce excessive amounts of leukemic white blood cells. In contrast, BCL2 inhibitors (e.g., venetoclax) block the BCL2 protein, which promotes leukemic cells to die through a process called apoptosis. Finally, monoclonal antibodies (e.g., rituximab, obinutuzumab) can attach to specific proteins on the cell surface of leukemic cells, preventing their growth. In CLL, the choice between these targeted therapies is based on the specific molecular and genetic characteristics of the disease and patient preference.
When CLL comes back it is called a relapse. For patients with a relapse, the treatment plan depends on how long the CLL has been in remission, the previous treatment and the effect it had, the genetic features of the disease, the general fitness of the patient and his/her personal wishes. In most cases, the treatment for patients with a disease relapse, or for patients without a response to first-line treatment (refractory patients) consists of targeted therapy. In fit patients with relapsed/refractory CLL, a stem cell transplantation can be considered. In addition to this, alternative treatment options can be offered through participation in a clinical trial.
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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