Chronic lymphocytic leukemia: Encyclopedia - Chronic lymphocytic leukemia

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (or "chronic lymphoid leukemia") CLL, is a cancer in which too many lymphocytes (a type of white blood cells) are produced.

CLL is the most-diagnosed form of leukemia in adults. Men are twice as likely to develop CLL as women, however the key risk factor is age: over 75% of new cases are diagnosed in patients over age 50. About 7300 new cases of CLL are diagnosed in the U.S. each year.

Chronic lymphocytic leukemia - Subtypes

CLL has two subtypes: B-cell and T-cell. The B-cell subtype is the most common form (about 95%) and shows up mainly in the bone marrow and blood. B-cell CLL is closely related to (and some may consider it the same as) a disease called small cell lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma expressed primarily in the lymph nodes. (It is likely that most cases referred to as T-CLL are large granular lymphocyte (LGL) leukemia. LGL leukemia is a chronic lymphoproliferative disorder with autoimmune features, many experts deny that T-cell CLL exists).

Chronic lymphocytic leukemia - Diagnosis

CLL is often incidentally discovered when a patient has a routine blood test. An excessive WBC (white blood cell) count is usually the first clue. The CLL diagnosis is confirmed by follow-up tests such as: differential WBC count which reveals high lymphocyte levels and the presence of abnormal cells; a specialized test called flow cytometry to detect the abnormal cells and determine their type; and sometimes also by bone marrow biopsy.

Some newly-diagnosed CLL patients have no clinical symptoms at all. Others report a general feeling of ill health, fatigue, low-grade fever, night sweats, joint pain, swollen lymph nodes, enlarged spleen, frequent infections, weight loss and loss of appetite.

A crucial part of the CLL diagnosis is determining the immunophenotype of the leukemia, that is, the abnormal proteins expressed by the leukemic cells. Flow cytometry is a very accurate immunophenotyping tool that identifies the presence or absence of specific protein antigens on blood or bone marrow cells.

The immunophenotype not only confirms the CLL diagnosis, but can also determine treatment. In B-cell CLL, an antigen called CD20 is often found on the leukemic cells. Using this information, researchers developed a monoclonal antibody drug called rituximab (Rituxan) to fight only CD20-positive cells.

Chronic lymphocytic leukemia - Stratification of risk of progression

Stratification of the risk of progression is becoming an accepted method of determining prognosis. This is done with the IgVH mutational status test, fluorescent in situ hybridization (FISH), and immunophenotyping for CD38 and ZAP-70 positivity. Patients with IgVH mutated CLL have a better prognosis than those with unmutated CLL. The FISH test looks for common chromosomal abnormalities—deletions of the 13q region have the best prognosis, followed by no detected deletions or "normal" karotype. Deletions of chromosome 12 are in the middle, with deletions of 11q signaling potentially aggressive disease. Deletions of 17p usually signal the most aggressive disease. CD38-negative patients have the better prognosis. The ZAP-70 test is still being standardized; those with ZAP-70 negative results have the better prognosis.

Chronic lymphocytic leukemia - Treatment

While considered incurable, CLL progresses slowly in most cases. Many people with CLL continue to lead relatively normal and active lives for many years - in some cases for decades. Because of its slow onset, early-stage CLL is generally not treated since it is believed that early CLL intervention does not improve survival time or quality of life. Instead, the condition is monitored over time.

The decision to start CLL treatment is taken when the patient's blood work and clinical symptoms indicate that the disease has progressed to a point where the patient can't function well. A "staging system" such as the Rai 4-stage system, the Binet classification and the immunophenotype are used to determine when and how to treat the patient.

CLL treatment focuses on controlling the disease and its symptoms rather than on an outright cure. CLL is treated by chemotherapy, radiation therapy, biological therapy, or bone marrow transplantation. Symptoms are sometimes treated surgically (splenectomy removal of enlarged spleen) or by radiation therapy ("de-bulking" swollen lymph nodes).

Initial CLL treatments vary depending on the exact diagnosis and the progression of the disease, and even with the preference and experience of the health care practitioner. There are dozens of agents used for CLL therapy, and there is considerable research activity studying them individually or in combination with each other. For example, the purine analogue fludarabine was shown to be superior to chlorambucil as primary therapy.^[1] Bone marrow transplantation is almost never used as a first-line treatement for CLL due to its risk. The monoclonal antibody, alemtuzumab (directed against CD52), may be used in patients with progressive disease.^[2]

Follow-up CLL treatments are sometimes used to lengthen time to relapse.

"Refractory" CLL is a disease that no longer responds favorably to treatment. In this case more aggressive therapies, including bone marrow transplantation, are considered.

Determining when to start treatment and by what means is often difficult; studies have shown there is no survival advantage to treating the disease too early. The National Cancer Institute Working Group has issued guidelines for treatment, with specific markers that should be met before it is initiated.

Adapted from the Wikipedia article "Chronic lymphocytic leukemia", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki