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 ("de-bulking" swollen lymph nodes).radiation therapy. 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. 

Decision to treat
While generally 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, in general, 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 to detect any change in the disease pattern.

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.

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.
  
Chemotherapy
Combination chemotherapy regimens are effective in both newly-diagnosed and relapsed CLL. Combinations of fludarabine with alkylating agents (cyclophosphamide) produce higher response rates and a longer progression-free survival than single agents:
  • FC (fludarabine with cyclophosphamide)
  • FR (fludarabine with rituximab)
  • FCR (fludarabine, cyclophosphamide, and rituximab)
  • CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)
Although the purine analogue fludarabine was shown to give superior response rates to chlorambucil as primary therapy, there is no evidence early use of fludarabine improves overall survival, and some clinicians prefer to reserve fludarabine for relapsed disease.

Alkylating agents approved for CLL include bendamustine and cyclophosphamide. Monoclonal antibodies, such as alemtuzumab (directed against CD52), rituximab (directed against CD20), and ofatumumab (Arzerra ) (directed against CD20) are also used. 

Stem cell transplantation
Allogeneic bone marrow (stem cell) transplantation is rarely used as a first-line treatment for CLL due to its risk. There is increasing interest in the use of reduced-intensity allogeneic stem cell transplantation, which offers the prospect of cure for selected patients with a suitable donor.

Younger patients that are at high risk for dying from CLL might consider hematopoietic stem cell transplantation (HSCT). Autologous stem cell transplantation, a lower-risk form of treatment using the patient's own blood cells, is not curative. 

Myeloablative (bone marrow killing) forms of allogeneic stem cell transplantation, a high-risk treatment using blood cells from a healthy donor, may be curative for some patients, but most patients cannot tolerate the treatment. An intermediate level, called reduced-intensity conditioning allogeneic stem cell transplantation, may be better tolerated by older or frail patients. 

Refractory CLL
"Refractory" CLL is a disease that no longer responds favorably to treatment. In this case more aggressive therapies, including lenalidomide, flavopiridol, and 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. 

Complications
Chronic lymphocytic leukemia may transform into Richter's syndrome, a term used to describe the development of fast-growing diffuse large B cell lymphoma, prolymphocytic leukemia, Hodgkin's lymphoma, or acute leukemia in a patient who has chronic lymphocytic leukemia. Its incidence is estimated to be around 5%

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