Patients with chronic lymphocytic leukemia (CLL) are at increased risk of infections as compared to age matched controls, with infections being a major cause of morbidity and mortality. Previous studies have shown that patients with CLL have both hypogammaglobinemia and impaired humoral immunity as defined by vaccine responses to both polysaccharide and peptide antigens. Attempts at decreasing infections in CLL have included therapy with prophylactic antibiotics and intravenous immunoglobulin. In general clinical practice and in previous studies, patients have started IV immunoglobulin replacement therapy if they have a history of serious infection or hypogammaglobinemia (defined as Immunoglobulin G below 500-600 g/dL), but vaccine responses have not been evaluated. This study will identify CLL patients with humoral immunodeficiency by checking both Ig levels and vaccines responses. In patients with impaired humoral immunity, the investigators will use subcutaneous immunoglobulin replacement to show this intervention will increase Ig levels, protective antibody titers, and be well tolerated.

Inclusion Criteria:

• Diagnosis of chronic lymphocytic leukemia
• Medically stable, with expected survival of > 1 year
• Able to understand and willingness to sign a written informed consent
• Able to comply with study procedures

Exclusion Criteria:

• Previously diagnosed primary immunodeficiency
• Additional immunosuppressive states as assessed by the primary or co investigators
• Ongoing therapy with Ig replacement
• Serum IgG < 500 mg/dL