What is chronic lymphocytic leukaemia?

Leukaemia is a haematological malignancy (blood cancer) that develops in the bone marrow, blood, the lymphatic system and other tissues. The leukaemia is commonly divided into acute and chronic leukaemia, depending on the rate of progression of the disease.


Generally, leukaemia is referred to in the presence of biological alterations in the blood cells (red cells, white cells and platelets) that cause growth and uncontrolled proliferation of the cells themselves. The name derives from the Greek word leukemia leucos, which means white because the disease begins in the white blood cells responsible for fighting infections, which normally reproduce according to the needs of the body.


In patients with leukaemia, the bone marrow produces large numbers of abnormal white blood cells, which have genetic mutations in the DNA that interfere with their function. The exact causes of this disease are unknown, but it appears to be influenced by both genetic and environmental factors.


Chronic leukaemia is more common in adulthood. The most common forms are chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). For both types of leukaemia it may more appropriate to use the word "enzootic" rather than leukaemia, given the clear differences in behaviour and response to therapy as well as prognosis in comparison to acute leukaemia.


CLL is the most common leukaemia in adults and the average age of onset is around 65 years. In some cases, its development is so slow that the disease remains dormant for years, with no obvious symptoms and sometimes without any need for treatment. This disease affects the lymphocytes, a particular group of white blood cells that help the body fight infections that accumulate in the peripheral blood, bone marrow and lymphoid organs.

What are the risk factors for chronic lymphocytic leukaemia?

There are no specific environmental factors or factors related to exposure to chemical or physical agents. Family history of the disease can increase the risk of the disease up to 3 times more than in people without a family history of leukaemia. The risk of CLL increases significantly with age; therefore, there are approximately 30 new cases per 100,000 inhabitants that are between the age of 80-85 years.


There are no specific prevention methods (lifestyle, eating habits, etc) for this disease.





How is chronic lymphocytic leukaemia diagnosed?

Chronic lymphocytic leukaemia (CLL) is frequently discovered by an incidental finding in the course of routine blood analysis, which show a high number of white blood cells (lymphocytes). In most cases, the patient with the increase in white blood cells enjoys full wellness. In rare cases, clinical symptoms or signs accompany the disease onset.


In 95% of cases the CLL originates from B-lymphocytes, while the remaining 5% by T lymphocytes. The CLL diagnosis must be carried out at a specialized centre of Haematology clinic through various testing, including:


  • Blood count that measures the number of white blood cells, platelets and red blood cells of the peripheral blood (PB) and details in percentage and absolute value of the five major types of white blood cells (neutrophils, eosinophils and basophils, monocytes and lymphocytes), whose morphological features may also be examined more thoroughly under a microscope. 
  • Bone marrow aspiration and biopsy: both procedures are performed safely by introducing a needle into a bone at the back of the pelvis, namely the posterior superior iliac spine. The bone marrow aspiration (AOS), once the needle is appropriately positioned under local anaesthesia, involves 2-4 short repeated aspirations that last a few seconds, in order to collect adequate samples of bone marrow. The bone marrow biopsy (BOM) is a procedure for the extraction of a small cylinder of bone marrow with a special instrument. It is always performed under local anaesthesia. The execution of AOS and the BOM for diagnosing CLL is strongly recommended before any treatment.
  • Morphological analysis: optical microscope is used to examine the morphology of bone marrow cells in samples of bone marrow aspiration and peripheral blood. It provides important information for the diagnosis and the definition of the stage of the disease.
  • Cytogenetics: this test is used to examine the number of chromosomes in the bone marrow cells and their structure in samples of bone marrow aspiration or peripheral blood. Certain specific chromosomal abnormalities may be associated with a poor prognosis. 
  • Immunophenotypic analysis: this analysis is used to examine the characteristics of the surface of CLL cells present in samples of bone marrow aspiration and/or peripheral blood, which facilitates the diagnosis and, in some cases, allows monitoring of the response to treatments over time. 
  • Molecular analysis is useful to examine the presence of "molecular markers" of the disease that can facilitate the prognostic classification and enable monitoring of the response to treatment over time. The "molecular markers" originate from chromosomal alterations or DNA. 
  • Lymph node biopsy: the laboratory analysis of a sample of a pathological lymph node allows one to determine the possible location of lymph in the lymphatic tissue CLL.




In many cases, the CLL can remain dormant and stable for many years without requiring treatment but only observation with periodic examinations. 


The progression of CLL can be associated to the appearance of symptoms among which the most common are asthenia (tiredness), weight loss and increased fatigability. Very frequently there is a progressive increase in peripheral lymphocyte counts, the superficial and deep lymph nodes, and sometimes the size of the spleen.


The progression of the disease is associated with a gradual weakening of the immune system, which exhibits a higher risk of infections. In some cases, concurrent autoimmune complications can occur that frequently occur with anemia or thrombocytopenia (platelets). Rarely, the disease can turn into a rapidly progressive form and acute ("Richter's Syndrome"). This evolution has a highly unfavourable prognosis.


Taking into consideration the slow rate of progression (the laziness) with which the disease usually progresses, it is very important, especially at the onset and in the initial phases of observation, to define the stage and complete a thorough study of the factors that determine the risk of progression and prognosis the CLL. These same tests can also indicate the best treatment among the many available, predict the response to it and determine in advance the likelihood of recurrence.


The staging of CLL follows two separate but integrated systems, RAI and BINET. Among the most important prognostic factors of CLL include:


  • Chromosomal abnormalities in particular the lack of the short arm of chromosome 17.
  • Mutational status of the immunoglobulin genes (IgVH): this is used to determine a more aggressive course (in the absence of mutation of genes) or a more favourable prognosis (in the presence of mutations in genes) of chronic lymphocytic leukaemia.
  • Study of the expression of beta-2-microglobulin, CD38 and ZAP-70: this can help predict the timing of progression from diagnosis to potential treatment. At Humanitas Cancer Center all the tests on bone marrow, peripheral blood or lymph node biopsies needed for staging and the definition of risk factors and prognosis are carried out.



What is the treatment for chronic lymphocytic leukaemia?

Treatment for chronic lymphocytic leukaemia is tailored to the patient's symptoms, disease stage and prognosis. In many cases without signs of progression of the disease a periodic observation for several years is sufficient without the need for any treatment. At the point at which therapy becomes necessary, the options include chemotherapy, therapy with monoclonal antibodies or a combination of both.


For certain patients, bone marrow transplantation (hematopoietic stem cells) from a donor (allogeneic) is becoming a popular option. Humanitas Cancer Center offers the following treatment options:


  • Note: Relative to the stage of chronic lymphocytic leukaemia, careful observation of the patient's condition and the execution of periodic blood tests and instrumental control are often an appropriate therapeutic approach. The progression from the initial stage can take several years, and the need for treatment is related to the appearance of clinical signs or symptoms such as the rapid growth in the number of lymphocytes and/or lymph nodes.
  • Chemotherapy: Currently, there are many chemotherapy drugs, which can be administered intravenously or orally. The goal of chemotherapy is to eliminate as many leukaemia cells as possible, paying much attention to the possible side effects and the infectious complications that may arise.
  • Monoclonal antibody therapy: Monoclonal antibodies are proteins produced artificially. Once administered intravenously or subcutaneously, these proteins are able to selectively target the leukemic cells by binding to them and activating mechanisms, which destroy the cells and protect healthy tissues.
  • Chemo-immunotherapy: One of the most significant therapeutic advances of recent years has been the development of a combination treatment of chemotherapy with monoclonal antibodies (chemo-immunotherapy), which results in a synergistic effect, and in a higher rate of clinical response.
  • Transplantation of hematopoietic stem cells: In people with a more aggressive form of recurrent or chronic lymphocytic leukaemia, this treatment has shown promising results and a growing recourse to hematopoietic stem cell transplantation from a donor (allogeneic). Allogeneic CLL provides therapy preparation (conditioning regimen) with a reduced intensity so individuals up to the age of 70-75 can be viable for transplant. The indication for transplant must be preceded by a careful evaluation of the clinical condition of the patient and a thorough analysis of the risks and benefits. Specialists at Humanitas Cancer Center have gained appropriate experience in the allograft with reduced intensity conditioning. The team for the treatment of chronic lymphocytic leukaemia is working closely with the team for transplantation of blood stem cells and bone marrow, in order to provide coordinated assistance to people undergoing transplant.