Leukemias

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is cancer of the cells called lymphocytes, a type of white blood cell. CLL cells start in the bone marrow and lymph nodes and then enter the bloodstream. Chronic leukemias, such as CLL, often do not cause problems for at least a few years but can be aggressive in some patients. Once symptoms appear or blood counts worsen, treatment usually begins immediately.

Lymphocytes develop in the bone marrow or lymph nodes from immature cells called lymphoblasts. Lymphoblasts mature into one of three types of lymphocytes: B lymphocytes, T lymphocytes or natural killer cells. In people with CLL, B lymphocytes that should stop dividing and die continue to multiply and live longer than normal cells, leading to an accumulation of these lymphocytes in the blood. As the CLL cells grow, they interfere with the normal production of healthy white blood cells, red blood cells and platelets.

Diagnosing CLL

In addition to a physical exam, blood, bone marrow and genetic tests may be used to diagnose CLL. These diagnostic tests can include the following:

  • Complete blood count (CBC) measures the number of white blood cells, red blood cells and platelets in the blood.
  • Flow cytometry helps determine whether an increase in lymphocytes is caused by CLL or another disorder.
  • Genetic tests can help determine whether chromosomal changes or gene abnormalities are present in CLL cells.
  • Bone marrow aspiration and biopsy are often done at the same time. During these procedures, bone marrow tissue samples are removed for examination. A bone marrow biopsy involves removal of a sample of marrow from within the bone (usually the pelvic bone). For bone marrow aspiration, liquid bone marrow is removed, usually from the back of the pelvic bone or the breastbone.

Imaging tests, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound and X-ray, are not necessary to diagnose CLL but may be done to help determine the extent of the disease.

Staging CLL

Most cancers are given a numbered stage based on the size of the tumor and how far the cancer has spread. CLL is given a numbered stage like other cancers, but the stage is not based on tumor size or extent.

The Rai staging system is the system most commonly used in the United States to stage CLL. It divides CLL into five stages based on the levels of lymphocytes, red blood cells and platelets and whether the lymph nodes, liver or spleen are enlarged (see Table 1). Stage 0 means CLL is present, but there is no enlargement of the lymph nodes, spleen or liver, and the red blood cell and platelet counts are normal. Stage IV, the most advanced stage, means CLL and thrombocytopenia (too few platelets) are present. In Stage IV, anemia and enlarged lymph nodes, spleen or liver may or may not be present. Stage 0 is considered low risk, Stages I and II are considered intermediate risk, and Stages III and IV are considered high risk. In recent times, more specific information can be gathered by genetic analysis of the CLL cells which can complement the staging system and help your doctor choose the best treatment option for you.

Table 1. Stages of CLL

Stage Description
Stage 0 The blood contains a significant number of cancer lymphocytes. Lymph nodes, spleen and liver are not enlarged, and red blood cell and platelet counts are near normal.
Stage I The blood contains a significant number of cancer lymphocytes, and lymph nodes are enlarged. The spleen and liver are not enlarged, and red blood cell and platelet counts are near normal.
Stage II The blood contains a significant number of cancer lymphocytes, and the spleen is enlarged. The liver and lymph nodes may or may not be enlarged, and red blood cell and platelet counts are near normal.
Stage III The blood contains a significant number of cancer lymphocytes and too few red blood cells (anemia). Lymph nodes, spleen and liver may or may not be enlarged. Platelet counts are near normal.
Stage IV The blood contains a significant number of cancer lymphocytes and too few platelets (thrombocytopenia). Anemia may or may not be present, and lymph nodes, spleen and liver may or may not be enlarged.
CLL risk levels:
Stage 0: low risk
Stage I and II: intermediate risk
Stage III and IV: high risk

Treating CLL

After CLL is diagnosed and staged, your health care team will work with you to choose the best treatment. Because CLL often grows slowly, people who have normal levels of red blood cells and platelets may be monitored without treatment (watchful waiting). Once treatment is needed, the main options are chemotherapy, immunotherapy and targeted therapy. Participating in a clinical trial is something that should definitely be considered by you and your physician.

Targeted therapy

Targeted therapy is considered a systemic treatment because the drugs travel throughout the body through the bloodstream. But targeted therapy works differently from chemotherapy; targeted therapy drugs seek out specific proteins on leukemia cells to block cancer growth and spread. Ibrutinib (Imbruvica), idelalisib (Zydelig) and venetoclax (Venclexta) are targeted therapy drugs used to treat CLL.

Chemotherapy

Chemotherapy drugs, also called cytotoxic drugs, are used to stop the growth of cancer, either by killing cancer cells or by preventing them from dividing and growing. Chemotherapy is also considered a systemic treatment because the drugs travel throughout the body in the bloodstream. This makes it useful for leukemia, which spreads throughout the body. Chemotherapy is sometimes referred to as conventional chemotherapy to distinguish it from targeted therapy, which also involves the use of drugs that travel throughout the body. It is given in cycles, with each treatment period followed by a rest period. Chemotherapy drugs often given for CLL include chlorambucil, cyclophosphamide (Cytoxan), fludarabine, bendamustine (Treanda) and pentostatin (Nipent).

Immunotherapy

Immunotherapy is an innovative approach that helps repair or stimulate a person’s own immune system to find and destroy cancer cells, much like it fights off foreign bacteria. Monoclonal antibodies are a type of immunotherapy used to treat CLL. They are laboratory-made versions of antibodies (proteins made by the immune system) that are designed to attach to proteins on the surface of cancer cells. Monoclonal antibodies for CLL include obinutuzumab (Gazyva), ofatumumab (Arzerra) and rituximab (Rituxan). Alemtuzumab (Campath) can also be rarely used in some patients.

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