Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia

DISEASE CHARACTERISTICS:

• Diagnosed B-cell chronic lymphocytic leukemia (CLL) defined by the National Cancer Institute (NCI) Working Group criteria
• Meets 1 of the following criteria:
• Binet stage C disease
• Binet stage B disease AND ≥ 1 of the following signs or symptoms*:
• B symptoms (night sweats, weight loss ≥ 10% within the previous 6 months, fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection), or constitutional symptoms (fatigue)
• Continuous progression (doubling of peripheral lymphocyte count within the past 6 months and absolute lymphocyte count > 50 G/I)
• Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia
• Massive, progressive or painful splenomegaly or hypersplenism
• Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter), danger of organ complications through large lymphoma (e.g., vascular compression or tracheal narrowing), or progressive lymphadenopathy
• Occurrence of symptomatic hyperviscosity problems at leukocyte counts > 200 G/I (symptomatic leukostasis) NOTE: * Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for eligibility
• No Binet stage A disease
• No transformation to an aggressive B-cell malignancy (e.g., diffuse large cell lymphoma, Richter's syndrome, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Cumulative Illness Rating Scale (CIRS) score > 6
• Life expectancy > 6 months
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase and transaminases ≤ 2 times ULN
• Creatinine clearance ≥ 70 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study treatment
• No known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs
• No cerebral dysfunction that precludes chemotherapy
• No active bacterial, viral, or fungal infection
• No clinically significant autoimmune cytopenia or Coombs-positive hemolytic anemia
• No other active malignancy requiring concurrent treatment except basal cell carcinoma or tumors treated curatively by surgery
• No medical or psychological condition that would preclude study therapy
• No concurrent disease that requires prolonged (> 1 month) therapy involving glucocorticoids

PRIOR CONCURRENT THERAPY:

• No previous treatment of CLL by chemotherapy, radiotherapy, or immunotherapy