Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed follicular non-Hodgkin lymphoma (NHL) meeting 1 of the
following criteria:

- Bulky (i.e., single mass ≥ 7cm in any uni-dimensional measurement) stage II
disease

- Stage III or IV disease

- WHO grade 1, 2, or 3a disease

- Bone marrow biopsies allowed provided they are submitted in conjunction with nodal
biopsies

- No fine-needle aspirates for diagnosis

- Tumor tissue must express the CD20-positive antigen by flow cytometry or IHC

- At least 1 site of measurable disease that is > 1 cm in diameter in ≥ 1 dimension
present either on physical exam or imaging studies

- Non-measurable disease alone not allowed, including the following:

- Bone lesions (lesions if present should be noted)

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Bone marrow (involvement by NHL should be noted)

- Low- or intermediate-risk disease by the Follicular Lymphoma International Prognostic
Index (FLIPI)

- FLIPI score meeting 1 or 2 of the following risk factors:

- Age > 60 years

- Involvement of > 4 nodal sites

- Stage III-IV disease

- Hemoglobin < 12.0 g/dL

- LDH normal

- Risk determined by the following:

- Low Risk: 0-1 of the above risk factors

- Intermediate Risk: 2 risk factors

- Poor Risk: ≥ 3 risk factors

- No known CNS involvement

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Creatinine clearance ≥ 30 mL/min

- Bilirubin ≤ 2 times upper limit of normal (unless secondary to Gilbert syndrome or
hepatic involvement of NHL)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Patients with HIV infection allowed provided the following criteria are met:

- No evidence of coinfection with hepatitis B or C

- CD4+ cell count ≥ 400/mm³

- No evidence of resistant strains of HIV

- HIV viral load < 10,000 copies HIV RNA/mL if not on anti-HIV therapy OR HIV
viral load < 50 copies if on anti-HIV therapy

- No history of AIDS-defining conditions

- No evidence of active hepatitis B (HBV) or C (HCV) infection (i.e., no positive
serology for anti-HBc or anti-HCV antibodies)

- HBV seropositivity allowed (HBsAg+) provided they are closely monitored for
evidence of active HBV infection by HBV DNA testing

- After completing treatment, HBsAg + patients must be monitored by HBV DNA
testing every 2 months for 6 months post-treatment, while continuing lamivudine
(required)

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy) for
NHL

- Prior involved-field radiation therapy allowed

- More than 2 weeks since prior corticosteroids except for maintenance therapy for a
non-malignant disease

- No concurrent dexamethasone or other steroids as antiemetics

- No live virus vaccination within 6 weeks prior to study entry

- No concurrent zidvoudine or stavudine