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Infection

Because chronic lymphocytic leukemia (CLL) affects the immune system and reduces the body's normal capacity to fight infection, CLL patients are prone to developing serious, life-threatening infections such as pneumonia (infection of the lungs) and septicemia (infection of the bloodstream). It has been estimated that up to 70% of patients with CLL will develop infections, and infections account for about 55% of deaths in patients with CLL. Prophylactic gammaglobulin therapy may be required to prevent serious infections in CLL patients. Once an infection develops, a variety of antibiotics may be used to control and eradicate the source of the infection. In addition, patients with chronic lymphocytic leukemia should be offered a pneumococcal vaccine (Pneumovax) at the time of diagnosis and every 5 years thereafter as well as an annual influenza vaccine. Patients with CLL who are treated with purine nucleoside analogues or alemtuzumab (a monoclonal antibody) should also receive prophylactic antibiotic therapy with sulfamethoxazole/trimethoprim to prevent Pneumocystis carinii pneumonia and an antiviral agent such as acyclovir to prevent Herpes virus infections.

Hematological Abnormalities

Chronic lymphocytic leukemia patients may develop a variety of hematological (blood) disorders, including:

• Anemia
• Pure red cell aplasia
• Thrombocytopenia

Anemia

This is a condition in which there is a lower than normal number of red blood cells in the bloodstream. Hemoglobin levels below 8 grams per deciliter usually require transfusion of packed red blood cells. Drugs, such as erythropoietin, that stimulate the production or red blood cells, may also be used.

Autoimmune hemolytic anemia (AIHA) is a form of anemia that is commonly associated with CLL and is estimated to occur in up to 37% of CLL patients. Autoimmune hemolytic anemia usually occurs in patients with advanced-stage CLL. In patients with AIHA, the immune system malfunctions and produces antibodies against the patient's own red blood cells resulting in the premature destruction of the red blood cells. Symptoms of AIHA include nosebleeds, bleeding gums, chills, fatigue, pallor, shortness of breath, rapid heart rate, jaundice, and swelling of the spleen (splenomegaly). Treatment options for patients who develop AIHA include:

• Corticosteroids (e.g., prednisone)
• Corticosteroids plus intravenous immunoglobulins (IVIG)
• Cyclosporine - if corticosteroids plus IVIG fail to improve the condition

Treatment options for patients with AIHA that is not responsive to the above treatments, a condition known as refractory AIHA, include:

• Alemtuzumab - alone or in combination with fludarabine
• Rituximab - alone or in combination with fludarabine and cyclophosphamide
• Radiation therapy to the spleen
• Surgical removal of the spleen (splenectomy)

Pure Red Cell Aplasia

Pure red cell aplasia is a condition in which there is a near absence of red blood cell precursors in bone marrow but with little or no abnormality in white blood cell or platelet production. This condition has been estimated to develop in up to 6% of patients with CLL. Treatment options for pure red cell aplasia include:

• Corticosteroids - usually used as initial therapy
• Corticosteroids plus cyclosporine
• Monoclonal antibodies - rituximab or alemtuzumab

Immune-Mediated Thrombocytopenia

Immune-mediated thrombocytopenia is a condition that develops when the body produces antibodies against a person's own platelets and results in an abnormally low number of platelets in the bloodstream (thrombocytopenia). Since platelets are the primary cells responsible for blood clotting, patients who develop immune-mediated thrombocytopenia are particularly susceptible to bleeding and/or bruising problems. It has been estimated that about 2% to 4% of patients with CLL develop immune-mediated thrombocytopenia. First-line therapy for immune-mediated thrombocytopenia is corticosteroids. Patients who do not respond to corticosteroids may be treated with mononclonal antibodies such as rituximab or alemtuzumab.

Secondary Cancers