Inclusion Criteria:

• Histologically confirmed follicular lymphoma grade 1, 2 or 3a.
• Patients previously untreated.

• Patients with at least one of the following symptoms requiring initiation of treatment:

  • Bulky disease at study entry according to the GELF criteria: nodal or extranodal mass > 7cm in its greater diameter
  • B symptoms
  • Elevated serum LDH or 2-microglobulin
  • involvement of at least 3 nodal sites (each with a diameter greater than 3 cm)
  • symptomatic splenic enlargement
  • compressive syndrome
  • pleural/peritoneal effusion
• Age must be > 18 years.
• Performance status < 2 on the ECOG scale (see appendix E).

• Adequate hematological function within 28 days prior to registration (unless those abnormalities are related to lymphoma extension), this includes:

  • Hemoglobin ≥ 8.0 g/dl (5.0 mmol/L)
  • Absolute neutrophil count (ANC) ≥ 1.5 109/L
  • Platelet count ≥ 100 109/L
• Women are not breast feeding, are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
• Having previously signed a written informed consent form.

Exclusion Criteria:

• Transformation to high-grade lymphoma (secondary to “low-grade” follicular lymphoma).
• Grade 3b follicular lymphoma.
• Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis).
• Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone.
• Patients with prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer.
• Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
• Poor renal function: Serum creatinine > 2.0 mg/dl (197 μmol/L),
• Poor hepatic function: total bilirubin > 2.0 mg/dl (34 μmol/L), AST (SGOT) > 3 x the upper limit of normal unless these abnormalities are related to lymphoma.
• Known HIV infection or active HBV or HCV infection.
• Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease). Judgment is up to the investigator.
• Life expectancy < 6 months
• Known sensitivity or allergy to murine products
• Treatment within a clinical trial within 30 days prior to trial entry
• Adult patient under tutelage.