Chronic lymphocytic leukemia (also called chronic lymphatic leukaemia or CLL) is a kind of chronic lymphoproliferative syndrome with leukaemic expression.

CLL is a cancer of the blood in which the bone marrow and the organs of the lymphatic system produce too many B lymphocytes, a kind of white blood cell. Under normal conditions the B and T lymphocytes are responsible for combatting infections, either by producing antibodies that attack the harmful elements that either invade or are produced by the organism (B lymphocytes), or by attacking them directly (T lymphocytes).

In CLL, the B lymphocytes progressively infiltrate the bone marrow, lymphatic tissues (mainly the lymph nodes and spleen) and other organs such as the liver. The clinical manifestations of the disease are the consequence of this infiltration which displaces the normal elements of the blood and impedes the correct functioning of the affected organs. Furthermore, the lymphocytes produced no not function correctly and are unable to fulfil their function of defending the organism.

CLL is the most frequent leukaemia in western countries (20-40% of all leukaemias), it being a rare disease in eastern countries. In Spain there are around 30 new case per million, per year.

Usually CLL affects people over the age of 60 (average age of 70; only 20% under the age of 65), it being extremely exceptional to find it in children, and it progresses very slowly. In many cases people with this disease present no symptoms for years. It is the only leukaemia for which a greater incidence has been described amongst family members (5%).

More than 80% of CLL patients are diagnosed by chance as a result of a routine blood test because the disease tends to be totally asymptomatic.

In the other cases the main symptoms can be: asthenia (weakness), lymphadenitis (swollen lymph nodes) and repeated infections. It is not unusual to observe splenomegaly (inflammation of the spleen) or hepatomegaly (enlargement of the liver), which can cause abdominal pains. Unlike the case of lymphomas, fever, night sweats and weight loss are not frequent (10%).

A morphological and immunophenotypic blood test is sufficient to diagnose CLL, although this is generally complemented by an examination of the bone marrow, obtained by means of puncturing the sternum or hip bone. For a correct evaluation its cytogenetic and molecular characteristics must also be analysed. A bone marrow biopsy (obtained from a cylinder of hip bone), the classic former exploration, is generally limited these days to patients under the age of 70 who require treatment. Similarly, it is not essential to perform a biopsy on one of the lymph nodes affected by lymphadenitis, unless CLL transformation to Richter syndrome is suspected (see prognosis). Imaging techniques are also often used to study the affected lymph node areas (X-rays, echographia, gammagraphy, scanner and magnetic resonance).

In Europe, Binet classification is usually employed to characterise CLL. Three different stages are distinguished according to the number of lymphatic tissue groups affected (lymph nodes in the neck, groin, armpit, spleen and liver) and whether the patient has anemia or not (low red blood cell count) or thrombopenia (very few platelets).

• Binet stage A: fewer then three areas of enlarged lymph nodes, no anemia, no thrombopenia.

• Binet stage B: three or more areas of enlarged lymph nodes, no anemia, no thrombopenia.

• Binet stage C: anemia and/or thrombopenia.

In the United States of America the Rai system, which is very similar, is more generally used to classify the disease.

Patients with CLL at the initial phase do not usually require treatment for years and can live a normal life, except for the regular tests they must have to see whether the disease is progressing or has remained stable.

The criteria for starting treatment are the presence of:

— Very obvious systemic symptoms (fever, sweating, loss of weight)

— Lymphadenitis or splenomegaly with great enlargement causing the patient pain

— Repeated infections

— Progressively increased anemia and/or thrombopenia

— Lymphocyte duplication occurs very rapidly (less than 12 months).

Very high levels of lymphocytes are not, in themselves criteria for starting treatment.

These patients must receive treatment with one of the multiple chemotherapy protocols currently in use, which are mostly based on a highly effective agent called fludarabine, associated with other chemotherapy agents (cyclophosphamide, mitoxantrone, chlorambucil, bendamustine, etc.) or a biotherapy agent such as Rituximab.

Biotherapy agents specifically attack leukaemia cells, practically without damaging healthy cells, by using monoclonal antibodies directed at specific cell receptors of the neoplastic cell. The most frequently used for CLL is the anti-CD20 monoclonal antibody Rituximab. The anti-CD52 antibody, Alemtuzumab, is usually reserved for relapsed cases.

Furthermore, these chemotherapies, as well as being tolerated quite well, are so effective that they can, on occasion, enable remission of the disease at the molecular level, a situation in which it is not possible to detect the disease, even with the most sophisticated laboratory techniques. Nevertheless, none of these treatments provides a cure for CLL, but the remissions achieved can be maintained for many years.

Unlike other leukaemias, given the advanced age of most patients, CLL is not usually treated with a transplant of hematopoietic progenitors. Young patients with an aggressive CLL may, however, benefit from this therapeutic procedure if they have a histocompatible donor, this being the only therapy that enables the disease to be cured. At the present time, older patients with a compatible donor are starting to be treated, with encouraging results, using a new kind of hematopoietic transplant called a reduced intensity transplant.

The autologous transplant of hematopoietic progenitors, although it was used for years with the aim of prolonging remission, has been practically abandoned since it never provides a cure and because of the availability of the new therapeutic protocols mentioned above.

Patients who have suffered a transformation to Richter syndrome must be treated as for an aggressive lymphoma (see Non-Hodgkin lymphoma).

The prognosis for patients with CLL is highly variable depending on the presence or absence of a series of prognostic factors such as: the stage of the disease; the time taken for the number of lymphocytes to double; the presence of certain cytogenetic alterations; an increase in certain serum markers, such as the expression of proteins ZAP-70 or CD38. Mutations in the variable region of the immunoglobulin genes identify two distinct types with regard to prognosis. Patients with mutations have a better prognosis because the disease tends to progress very slowly and they do not require treatment and can live for many years. In contrast, CLL that does not present this mutation tends to progress more rapidly, and has a worse prognosis.

5-10% of CLL patients suffer an evolution to an aggressive kind of lymphoma called Richter syndrome, which requires intensive chemotherapy.

A small percentage of patients (5%) present (either before or after diagnosis for CLL) secondary neoplasms (skin, gastrointestinal tract or lung).

For more quality information about chronic lymphocytic leukemia you can consult the following websites:

• What Is Chronic Lymphocytic Leukemia?. American Cancer Society

• Chronic Lymphocytic Leukemia Treatment. National Cancer Institute

• Chronic lymphocytic leukemia (CLL). Leukemia and Lymphoma Society
  
  
• Types of CLL Treatment. Leukemia and Lymphoma Society

There are other resources and links of interest that may be of use to chronic lymphocytic leukemia patients:

 

• Bone marrow transplant guide. Fundación Josep Carreras

• Graft-versus-host disease. Leukaemia and Lymphoma Society

• Fertility and treatment information. Leukaemia and Lymphoma Society