Chronic Lymphocytic Leukemia (CLL) is a cancer of lymphocytes, a type of white blood cell that is normally part of the immune system. It is the most common leukemia in the Western world, with about 15,000 new cases of CLL diagnosed in the United States annually. It is estimated that some 100,000 people in the US are living with the disease. CLL is more common in people who are over the age of 60.
Lymphocytes are a component of the normal immune system that helps fight infection. There are two principal kinds of lymphocytes, B cells and T cells, which function to make antibodies (B cells) and to regulate the immune system and directly eliminate infected or diseased cells (T cells). Both are initially produced in the bone marrow, T cells mature in the thymus, and both subsequently circulate in the blood and through the lymph nodes and spleen. In CLL patients, a single mature B or T lymphocyte becomes cancerous and begins to slowly divide and expand, which crowds out the normal diverse populations of these cells. The lymphocytes that are made also don’t work effectively. This can affect the function of the immune system, sometimes making people with CLL prone to certain infections. Because the immune system is unregulated, people with CLL can develop autoimmune disorders with destruction of the patient’s own platelets and red blood cells. If enough of these lymphocytes are made, they can crowd the bone marrow and affect the body’s ability to make red blood cells that carry hemoglobin (important for oxygen circulation) and platelets (important for control of bleeding). Lymphocytes can also fill the lymph nodes which can cause the lymph nodes to enlarge, as well as the liver and spleen.
Symptoms of CLL
Many people with CLL have no symptoms and the diagnosis is made by an elevated lymphocyte count on a routine blood test. Sometimes patients may note one or more enlarged lymph nodes, which are usually painless. The disease can also cause recurrent fevers, chills and night sweats. If the hemoglobin is low due to autoimmune destruction of the red blood cells or from crowding in the bone marrow, fatigue can occur. If the platelet count is low due to autoimmune destruction of the platelets or from crowding in the bone marrow, bleeding and bruising can occur.
Risk Factors of CLL
Generally, there are no known risk factors for CLL; however there can be a predisposition to CLL if several family members already have it. For reasons that are not understood, CLL is much less common in Asia and persons of Asian descent.
How CLL is Diagnosed
Frequently, CLL is found on routine blood work since most people with CLL may have no symptoms. If there are abnormalities on routine blood work, special testing is done to confirm the diagnosis. One of the tests used is flow cytometry to measure proteins that are expressed on the outside of the cell and are typical of CLL. In addition, FISH (fluorescence in-situ hybridization) is a test that can look at changes in the chromosome of the cancer cells. Certain abnormalities of the chromosomes can predict for a milder or more aggressive form of the disease, and may influence which treatment is chosen. A bone marrow biopsy is usually done to determine whether the marrow is involved and to get a more complete picture of the chromosomes at diagnosis.
Each patient with CLL will have routine CAT scans, which may be necessary periodically, to measure enlarged lymph nodes as well as the liver and spleen which can also become enlarged.
Treatment Options for CLL at Tufts Medical Center
The goal of treatment of CLL is to minimize symptoms or complications of the disease; therefore, many people with CLL may never need treatment. Reasons to consider treatment of CLL include but are not limited to:
• If the immune system is severely affected causing frequent infections.
• If the red blood cells or platelets are decreased, causing fatigue or bleeding complications.
• If the lymph nodes or spleen are significantly enlarged.
• If the patient is having recurrent fevers, chills, night sweats or weight loss.
Certain high risk features in CLL have been identified which can predict whether a patient will do worse and have an accelerated course. Those markers will be checked at disease presentation and during the course of the disease. Those patients may be candidates to undergo a bone marrow stem cell transplant early in the course of disease, before the leukemia has become resistant.
Treatment for CLL is usually in the form of chemotherapy. Two common chemotherapy regimens are fludarabine, cyclophosphamide and rituximab (FCR) or pentostatin, cyclophosphamide and rituximab (PCR). Alternatively, bendamustine with rituximab is now being used. Alemtuzumab is a monoclonal antibody which also offers a treatment option. If the CLL returns after different chemotherapy regimens have been tried, a bone marrow stem cell transplant or a clinical trial should be considered. Since CLL frequently is a disease seen in older patients, the reduced intensity preparative regimen for transplantation that was developed at Tufts is particularly suited to provide this therapy to older patients. A transplant is the only cure for CLL at that stage.
Tufts Medical Center also participates in a nationwide trial with a new monoclonal antibody in patients with advanced CLL. This antibody is unique in that it is smaller than the currently available antibodies and can penetrate lymph nodes much better.
Programs + Services
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Research + Clinical Trials
The purpose of this study is to see if GS-9973 can benefit subjects with CLL, MCL, DLBCL, FL and other iNHLs. This study will also investigate how safe GS-9973 is and how well the drug is tolerated.
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This is a non-randomized, open-label study evaluating the safety and efficacy of pembrolizumab (MK-3475) used in combination with dinaciclib (MK-7965) in the treatment of relapsed or refractory chronic lymphocytic leukemia (rrCLL), multiple myeloma (rrMM), or diffuse large B-cell lymphoma (rrDLBCL) in up to 138 participants from multiple sites.
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