Early or Delayed Fludarabine and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

DISEASE CHARACTERISTICS:

• Clinical and immunophenotypic evidence of B-cell chronic lymphocytic leukemia (CLL) diagnosed within the past 6 months AND meets the following criteria:

  • An absolute lymphocytosis of > 5,000/μL
  • Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes

  • Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers

    • B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density
    • Patients with bright surface immunoglobulin levels must have CD23 coexpression and absence of t(11;14) on interphase cytogenetics or have negative tumor protein staining for cyclin D1
• Low-risk category (i.e., only stages 0 or I) of the modified three-stage Rai staging system

• No evidence of active or progressive disease as demonstrated by any of the following:

  • Massive or progressive splenomegaly and/or lymphadenopathy that requires therapy
  • Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 6 months
  • Presence of weight loss > 10% over the preceding 6-month period
  • Grade 2 or 3 fatigue
  • Fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection
  • Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/μL)

• Must have undergone IgV_H mutation testing and be classified according to the following:

  • Genetically low-risk disease

    • IgV_H mutated
    • Less than 98% IgV_H homology

  • Genetically high-risk disease

    • IgV_H unmutated
    • At least 98% IgV_H homology

PATIENT CHARACTERISTICS:

• Performance status 0-1
• Creatinine ≤ 1.5 times upper limit of normal
• No HIV disease
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior therapy for CLL, including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
• No concurrent hormones or other chemotherapy except for steroids for hypersensitivity reactions or new adrenal failure (chronic requirement for steroids is an exclusion criterion for this study) or hormones for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent palliative radiotherapy