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Chronic Lymphocytic Leukemia (CLL)

The unpleasant truth is that CLL is probably "incurable" by present treatments. But, fortunately, a large group of CLL patients do not require therapy. Studies suggest that people with Stage A CLL (that is, individuals who have fewer than three areas of enlarged lymphoid tissue) do not benefit from early treatment. They may, in fact, suffer drawbacks because of it. Therefore, most oncologists base CLL treatment upon both the stage and symptoms of the patient.

For example, in older patients (60+ years) who have low-risk, early stage disease (Rai Stage 0) a conservative "watch and wait" approach may be taken.

By contrast, older individuals with CLL-related complications or more advanced disease (Rai Stage III or IV) may benefit from chemotherapy and treatment with a corticosteroid (e.g., prednisone, prednisolone).

Corticosteroids are first-line agents for people in whom the immune systems has been altered by CLL. CLL may cause autoimmune syndromes in which the patient's immune system attacks and destroys his or her own blood cells. When the red blood cells are affected, the condition is known as immunohemolytic anemia, characterized by decreased numbers of red blood cells, which may cause fatigue, dizziness, and shortness of breath. When the blood platelets are affected, it is called immune-mediated thrombocytopenia, in which a decreased numbers of platelets may lead to bleeding).

For younger patients who are experiencing symptoms, the physician may consider early chemotherapy, plus allogeneic or autologous bone marrow transplantation (alloBMT; autoBMT).

In general, the indications for treatment are:

• falling hemoglobin or platelet count
• progression to a later stage of disease
• painful, disease-related overgrowth of lymph nodes or spleen
• lymphocyte doubling time (an indicator of lymphocyte reproduction) of fewer than 12 months
• transformation of CLL to high-grade disease or aggressive non-Hodgkin's lymphoma

If the patient experiences blood flow problems caused by high numbers of leukemia cells in the circulation, the physician may recommend leukapheresis, also known as apheresis, to separate out white blood cells, prior to chemotherapy.

Symptoms that are related to enlargement of the lymph nodes in one area or an overgrown spleen may be treated by localized, low-dose radiotherapy, or surgical management by splenectomy (removal of the spleen). But if leukemia has invaded the lymph nodes at many different sites, total body irradiation (TBI) may be needed.

The chemotherapeutic plans that are used most often for CLL are:

• combination chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) plus a corticosteroid drug such as prednisone, or
• single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine (2-chlorodeoxyadenisine; 2-CDA). However, such drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.

People with intermediate (Rai Stage I and II) or advanced (Rai Stage III or IV) disease may be helped by participation in a clinical trial. At the present time, clinical trials are being conducted using immunologic compounds (e.g., interferons, monoclonal antibodies) as well as new chemotherapeutic agents (e.g., bryostatin, dolastatin 10, and PSC 83 - a cyclosporine drug given with chemotherapy to overcome drug resistance).

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