• Changes in lymphocyte gene expression as measured by DNA microarray analysis during and after completion of study treatment [ Designated as safety issue: No ]
  
• Gene expression of leukemic cells in blood, bone marrow, and lymph nodes as measured by DNA microarray analysis [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Evaluate changes in lymphocyte gene expression by DNA microarray analysis in patients with intermediate- or high-risk untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) treated with rituximab and fludarabine.
• Evaluate gene expression of leukemic cells in blood, bone marrow, and lymph nodes by DNA microarray analysis.

Secondary

• Correlate gene expression analysis with the presence or absence of somatic mutations in tumor cells (e.g., p53 mutations or deletions) and clinical parameters.
• Analyze protein expression using various proteomic approaches and the presence or absence of protein modifications in relation to gene expression profiles, CLL/SLL behavior, and treatment response.
• Evaluate lymphocytes for gene expression by DNA microarray analysis and for chromosomal karyotyping by banding and FISH techniques and by multicolor immunophenotyping.
• Correlate PET scan with gene expression profile in leukemic cells and with biologic and prognostic markers of CLL/SLL.
• Understand the biology and treatment of CLL/SLL.

OUTLINE: Patients receive rituximab IV over 2-8 hours on day 1 and fludarabine IV over 30 minutes on days 1-5 (days 2-6 of cycle 1 only). Treatment repeats every 28 days for up to 4-6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 and 6 months and then at 1 and 2 years.

PROJECTED ACCRUAL: Approximately 105 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

• Meets one of the following criteria:

  • Intermediate-risk disease

    • Stage I: Elevated lymphocyte count with enlarged lymph nodes
    • Stage II: Elevated lymphocyte count with enlarged spleen or liver

    • Stage I or II: Active disease, as evidenced by at least 1 of the following criteria:

      • Massive progressive splenomegaly or lymphadenopathy
      • More than 10% weight loss within the past 6 months
      • Constitutional symptoms of extreme fatigue, night sweats, recurrent fever of more than 100 degrees F (documented fevers must be occurring without evidence of specific infection), or bone pain
      • Progressive lymphocytosis with an increase of more than 50% over a 2 month period or an anticipated doubling time of less than 6 months
      • Chronic infections, defined as either an increased number of infections or prolonged infections
      • Other high-risk prognostic indicators (e.g., excess elevation of β-2-microglobulin, CD38 expression, or adverse cytogenetics)

  • High-risk disease

    • Stage III: Elevated lymphocyte count with anemia (hemoglobin less than 11 g/dL)
    • Stage IV: Elevated lymphocyte count with thrombocytopenia (platelet count less than 100,000/mm^3)
• Patients with a diagnosis of CLL or SLL who do not meet eligibility criteria for receiving treatment with rituximab and fludarabine may enroll on this study for the purpose of donating cellular products

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• No active autoimmune hemolytic anemia or immune thrombocytopenia

Hepatic:

• AST and ALT no greater than 2.0 times normal (unless due to liver disease)
• Bilirubin no greater than 2.0 mg/dL (unless due to Gilbert's disease)

Renal:

• BUN no greater than 1.5 times normal
• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance greater than 50 mL/min

Other:

• No medical condition that requires chronic use of corticosteroids
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior monoclonal antibody therapy

Chemotherapy:

• No prior cytotoxic chemotherapy

Endocrine therapy:

• Prior steroid therapy to control autoimmune hemolytic anemia or immune thrombocytopenia is allowed provided:

  • No current requirement for maintenance steroids
  • No current evidence of active autoimmune disease
  • Direct Coombs' test currently negative
• No concurrent corticosteroids as prophylactic antiemetic therapy

Radiotherapy:

• Not specified

Surgery:

• Not specified