RATIONALE: Studying PET scans given to patients with cancer who are undergoing treatment may help doctors predict how patients will respond to treatment.

PURPOSE: This clinical trial is studying PET scans in patients with diffuse large B-cell lymphoma who are receiving rituximab together with cyclophosphamide, doxorubicin, vincristine, and prednisone.

OBJECTIVES:

Primary

• To evaluate if an early positive positron emission tomography (PET) scan after 2 courses of rituximab with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone can be used to identify a group of patients having a poor prognosis.

Secondary

• To compare modified PET/CT scan response criteria with revised standard response criteria.
• To evaluate, in a prospective manner, whether a proliferation-inducing ligand (APRIL) expression is a prognostic factor in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Rituximab IV alone is continued for an additional 2 courses after completion of the initial 6 courses.

Patients undergo positron emission tomography (PET) scan prior to and after completion of study therapy. Patients also undergo PET scan after course 2, and those with a positive PET result undergo an additional PET scan after course 4.

Previously collected tumor samples are analyzed for a proliferation-inducing ligand (APRIL) expression.

After completion of study treatment, patients are followed periodically for up to 5 years.

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed diagnosis of CD20+ diffuse large B-cell lymphoma (DLBCL)

  • Stage I-IV disease
  • All IPI risk groups

• Must be positron emission tomography (PET)-positive

• At least one measurable lesion ≥ 15 mm in its shortest axis (greatest transverse diameter) for jugulodigastric and infra-carinal lymph nodes with CT scan (MRI is allowed only if CT scan cannot be performed)

  • Otherwise the shortest axis (greatest transverse diameter) must be ≥ 10 mm

  • Lesions should be selected according to the following features:

    • Clearly measurable in two perpendicular dimensions
    • From as disparate regions of the body as possible
    • Include mediastinal and retroperitoneal areas of disease whenever these sites are involved

Exclusion criteria:

• Secondary DLBCL (in transformation)
• Evidence of symptomatic CNS disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG or WHO performance status 0-2
• Cardiac ejection fraction ≥ 50% as assessed by echocardiography
• Sufficient hematological values, hepatic and renal function
• Patient condition, compliance, and geographic proximity must allow proper staging and completion of treatment and follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study therapy

Exclusion criteria:

• Prior or concurrent hematological malignancies

  • Patients who have had prior solid organ tumors that required no treatment over the past 5 years and are currently disease-free are allowed

• Unstable cardiac disease within the past 6 months

• Any serious underlying medical condition (at the judgment of the investigator) that could impair the ability of the patient to participate in the study (e.g., active autoimmune disease, uncontrolled diabetes, HIV- and hepatitis-infection)

• Known hypersensitivity to any component of the study drugs

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

• Prior chemotherapy, radiotherapy, or immunotherapy (e.g., rituximab) for lymphoma

• Prior anthracycline treatment

• Concurrent radiotherapy

• Concurrent regular corticosteroids in the past 4 weeks

  • Doses ≤ 20 mg/day of prednisone for indications other than lymphoma or lymphoma-related symptoms allowed

• Concurrent drugs contraindicated for use with the study drugs according to the Swissmedic-approved product information

• Other concurrent experimental drugs or other anticancer therapy