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.

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).

Clinical features

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

Diagnosis

CLL is often discovered incidentally 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 a raised lymphocyte count and the presence of "smear" or "smudge" cells on microscopy; a specialized test called flow cytometry to detect the abnormal cells and determine their type; and sometimes also by bone marrow biopsy.

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

Risk stratification

Laboratory stratification of the risk of progression can provide an indication of prognosis. Prognostic indicators include IgVH (immune globulin heavy chain variable region) mutational status, cytogenetic analysis using fluorescent in situ hybridization (FISH), and immunophenotyping for CD38 and ZAP-70 positivity. Cases with mutated IgVH tend to have a better prognosis than those with IgVH-unmutated CLL. FISH analysis looks for recurrent chromosomal abnormalities—cases with deletions of the 13q region have the best prognosis, followed by those with no detected deletions or a "normal" karotype. Deletions of chromosome 12 have an intermediate prognosis, with deletions of 11q signaling potentially aggressive disease. Deletions of 17p usually signal the most aggressive disease. On immunophenotyping, CD38-negative patients have a better prognosis. ZAP-70 expression as measured by immunophenotyping correlates well with IgVH mutation status; those with ZAP-70 negativity usually have mutated IgVH, and a better prognosis.

Treatment

Whilst considered incurable, CLL progresses slowly in most cases. Many people with CLL lead 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 clinical symptoms or blood counts indicate that the disease has progressed to a point where it may affect the patient's quality of life. Clinical "staging systems" such as the Rai 4-stage system and the Binet classification can help 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, although the purine analogue fludarabine was shown give superior response rates than chlorambucil as primary therapy, there is no evidence that fludarabine improves overall survival, and some clinicians prefer to reserve fludarabine for relapsed disease. Combination chemotherapy regimens such as fludarabine with cyclophosphamide, FCR (fludarabine, cyclophosphamide and rituximab) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) are effective in both newly-diagnosed and relapsed CLL. Allogeneic bone marrow (stem cell) transplantation is rarely used as a first-line treatment for CLL due to its risk.

"Refractory" CLL is a disease that no longer responds favorably to treatment. In this case more aggressive therapies, including bone marrow (stem cell) transplantation, are considered. The monoclonal antibody, alemtuzumab (directed against CD52), may be used in patients with refractory, bone marrow-based disease. There is increasing interest{citation needed}} in the use of reduced intensity allogeneic stem cell transplantion, which offers the prospect of cure for selected patients with a suitable donor.

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.

References

External links

Online CLL Support Forums:

CLL Forum - a moderated forum-based global community providing support and guidance to people living with CLL and their caregivers.

Hematology

Chronische lymphatische Leukämie | Leucémie lymphoïde chronique | Kronisk lymfatisk leukemi