• Anti-pneumococcal IgG serum level > 250 mg of antibody nitrogen/ml will be
• considered protective. Measurement of antibody response will include either
• radioimmunoassay or serotype-specific antibodies by enzyme-linked immunosorbent
• assay. The antibody levels will be checked on the day of vaccination; one and
• 3 months after vaccination is given.

Primary Objective:

1. To evaluate efficacy of GM-CSF-mediated enhanced seroconversion (protective anti-pneumococcal serum immunoglobulins) in patients receiving conventional 23-valent capsular polysaccharide pneumococcal vaccine (PPV) and 7-valent Pneumococcal conjugated vaccine (PCV7) while undergoing treatment for advanced chronic lymphocytic leukemia (CLL).

Secondary Objective:

1. To evaluate the effect of GM-CSF on the dendritic cells and cytokine production in CLL patients.

Sargramostim (also commonly called granulocyte macrophage colony stimulating factor - GM-CSF) is a medication used to stimulate the bone marrow production of white blood cells before a stem cell transplant, after chemotherapy or after a bone marrow transplant. Pneumococcal vaccine is a medication used to prevent infections caused by a bacteria called Streptococcus pneumoniae.

If you have not had a gammaglobulins test (a test to measure immunity against certain infectious diseases) measured within three months before the study begins, then this blood test will be done before you receive any study medications.

Women who are able to have children must have a negative urine pregnancy test before starting treatment.

After consenting to this study, you will be randomly assigned(as in the toss of a coin) to receive treatment with sargramostim in addition to the pneumococcal vaccine or to receive pneumococcal vaccine alone (Prevnar).

If you are randomized to vaccine plus sargramostim group, you will receive an injection of sargramostim at the same time you receive the pneumococcal vaccine.

If you are randomized to the vaccine alone group, you will receive the pneumococcal vaccine on the first day.

Blood tests will be performed on the day of the pneumococcal vaccination, and 4 weeks, 12 weeks and 24 weeks after vaccination. Each of the blood tests will require about 4 teaspoons of blood. These blood tests will measure your immunity to pneumococcal infection.

If after 6 months of your first vaccination your body is not able to show immunity to pneumococcal infection, you will receive a second dose either pneumococcal vaccine plus sargramostim or pneumococcal vaccine alone. Your immunity will be checked again at 4 weeks, 12 weeks, and 24 weeks after this second dose. Only 4 teaspoon of blood will be required for the tests.

You may be removed from the study if you have a severe allergic reaction to the sargramostim and/or pneumococcal vaccine. The total maximum time you will be on this is study is 24 months.

This is an investigational study. Both of the medications used in this study are approved by the FDA. Up to 50 patients may be treated on this study. All will be enrolled at M.D. Anderson.

• Drug: Sargramostim
• Biological: Pneumococcal Vaccine

• Experimental: Pneumococcal Vaccine + Sargramostim
• Experimental: Pneumococcal Vaccine Alone

Inclusion Criteria:

• Patients with Rai stage (0 to 4) CLL.
• No prior Campath or fludarabine-based therapy within 12 months.
• No prior Rituximab® within 6 months.

Exclusion Criteria:

• Patients will not be entered while neutropenic (PMNs < 500 cells/mm3).
• Patients will not be entered while febrile (T > 38 degrees C) within 1 week.
• Active infection.
• Patients with known HIV infection.
• Known history of allergy to GM-CSFor pneumococcal vaccine.
• Chemotherapy other than Campath, fludarabine, cyclophosphamide, in 4 weeks.
• Patients who have previously received pneumococcal vaccine within the preceding 12 months.
• Absolute lymphocyte count less than 500 cells/mm3