RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving pentostatin together with cyclophosphamide and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving pentostatin together with cyclophosphamide and rituximab works in treating patients with previously untreated chronic lymphocytic leukemia.

OBJECTIVES:

• To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab.
• To characterize the toxicity of this regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 3 months for 1 year.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells

  • Previously untreated disease

• Meets 1 of the following risk criteria as defined by the three-stage Rai system

  • Intermediate-risk disease

    • Must meet the criteria for active disease as defined by the NCI Working Group guidelines including the following:

      • Weight loss
      • Fatigue
      • Fevers
      • Evidence of progressive marrow failure
      • Splenomegaly
      • Progressive lymphadenopathy
      • Progressive lymphocytosis with a rapid doubling time

  • High-risk disease

• Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis

• Patients with small lymphocytic lymphoma (CLL type) are eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin)
• Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage

Exclusion criteria:

• Significant active infections

• Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

  • Patients who are hepatitis B antibody positive are eligible for this protocol

PRIOR CONCURRENT THERAPY:

• Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
• No prior cytotoxic therapy or rituximab for this cancer
• No concurrent radiotherapy or other chemotherapy