Chronic lymphocytic leukemia

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

CLL has two subtypes: T-cell and B-cell. The latter (B-cell) 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.

CLL is the second-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.

Diagnosis

CLL is often discovered by chance 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 abnormal, immature cells; a specialized test called flow cytometry to detect the mutated cells and determine their type; and usually 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 actual type of genetic defect expressed in the leukemic cells. Flow cytometry is a very accurate immunophenotyping tool that identifies the presence or absence of specific antigens on blood or bone marrow cells.

The defect type not only confirms CLL diagnosis but also determines treatment. With a known defect, it may be possible to design a drug that targets cells with this defect. 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 rituxiamb (Rituxan) to fight only CD20-positive cells.

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 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 and the immunophenotype are used to determine when and how to treat the patient.

CLL treatement 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 (remove enlarged spleen) or by radiation ('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's considerable research activity studying them individually or in combination with each other. Bone marrow transplantation is almost never used as a first-line treatement for CLL due to its risk and in no small measure, its cost.

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

'Refractory' (or indolent) CLL is disease that no longer responds favorably to treatment. In this case more aggressive therapies, including bone marrow transplantation, are considered.