RATIONALE: Analyzing genes that are present in cancer cells may be useful as a method for predicting the response of non-Hodgkin's lymphoma to cancer treatment. Imaging procedures such as positron emission tomography (PET) scans may improve the ability to measure how well cancer has responded to treatment.

PURPOSE: This phase II trial is studying molecular risk assessment to see how well it works in predicting response to therapy in patients who are receiving treatment for non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine whether molecular risk assessment can identify groups of patients with diffuse large B-cell non-Hodgkin's lymphoma (NHL) who will demonstrate at least 50% difference in early response rates to treatment as determined by positron-emission tomography (PET) imaging.
• Determine, by PET imaging, the response rate of patients treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab.
• Determine whether early response rates can be predicted by gene expression profiles at diagnosis in these patients.
• Compare gene expression profiles of patients with refractory or relapsed large cell NHL with profiles of the disease at diagnosis.
• Determine relapse-free and overall survival rates of these patients.
• Determine the feasibility of a new NHL treatment algorithm based on prognostic index and molecular risk, and early response assessment by PET imaging.

OUTLINE: Molecular risk assessment is performed using lymph node tissue from initial diagnosis to test for "activated" genes before starting treatment.

Patients receive rituximab IV over 3-6 hours, cyclophosphamide IV over 30 minutes, doxorubicin IV over 5 minutes, and vincristine IV over 5 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3-8 courses. Patients undergo whole-body positron-emission tomography (PET) scanning at baseline and after course 3 to determine response. Results from the genetic testing and PET scans are used to determine further treatment recommendations.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 36-50 patients will be accrued for this study.

• Biological: rituximab
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate
• Genetic: microarray analysis

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma
• CD20 and/or CD19 positive by immunohistochemistry or flow cytometry
• Disease evaluable by positron-emission tomography scan
• Diagnostic tissue (either frozen or fresh unfixed) available for molecular testing or willing to undergo a repeat procedure to obtain such tissue
• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine no greater than 3 mg/dL

Cardiovascular

• LVEF at least 40%

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No significant organ dysfunction that would preclude study chemotherapy
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy
• No prior biological response modifier therapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No prior radioimmunotherapy

Surgery

• Not specified