• Negative [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan after 2 cycles of R-CHOP [ Time Frame: 2 cycles of R-CHOP ] [ Designated as safety issue: Yes ]
  

• Response after six cycles of R-CHOP [ Time Frame: 6 Cycles of R-CHOP ] [ Designated as safety issue: No ]
  
• progression free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  
• Grade 3-4 toxicity [ Time Frame: 6 cycles of R-CHOP ] [ Designated as safety issue: Yes ]
  

Genetic: Blood draw
Patients will have a blood sample collected for genotyping of the FCGR3A gene (immunoglobulin Fc G receptor IIIa), the ABCB1 gene (ATP Binding Cassette Beta 1; also called MDR1), and other candidate genes. Patients will be treated with R-CHOP for six cycles, which is standard therapy for advanced stage DLCL. Response will be monitored by an FDG-PET scan performed after 2 cycles of R-CHOP and restaging exams performed upon completion of chemotherapy. Gene polymorphisms will be analyzed to establish which polymorphisms predict response to R-CHOP.
Drug: Rituximab
Rituximab, 375 mg/ m2 IV Day 1, Treatment will be repeated every 21 days.
Drug: Cyclophosphamide
Cyclophosphamide 750 mg/ m2 IV Day 1, q 21 days
Drug: Doxorubicin
Doxorubicin 50 mg/ m2 IV Day 1, q 21 days
Drug: Vincristine

Vincristine* 1.4 mg/ m2 IV Day 1, q 21 days

*Maximum dose of vincristine is 2 mg

Drug: Prednisone
Prednisone 100 mg PO Days 1-5, q 21 days

Upon enrollment in the study, patients will have a blood sample collected for genotyping of the FCGR3A gene (immunoglobulin Fc G receptor IIIa), the ABCB1 gene (ATP Binding Cassette Beta 1; also called MDR1), and other candidate genes. Patients will be treated with R-CHOP for six cycles, which is standard therapy for advanced stage DLCL. Response will be monitored by an FDG-PET scan performed after 2 cycles of R-CHOP and restaging exams performed upon completion of chemotherapy. Gene polymorphisms will be analyzed to establish which polymorphisms predict response to R-CHOP.

Inclusion Criteria:

• Histologically proven diffuse large B-cell non-Hodgkin's lymphoma according to the WHO classification, with measurable or evaluable disease
• No prior therapy for NHL. Patient may be enrolled in this study after the first cycle of R-CHOP if all screening evaluations were performed prior to the first cycle of chemotherapy.
• Ann Arbor stage 3 or 4
• Age greater than or equal to 18 years
• Patient must give written informed consent.
• A patient enrolled in another clinical trial may also enroll in this study if the other trial has an R-CHOP treatment arm and the patient is randomized to the R-CHOP only arm. Registration to this study must occur after randomization in the other trial.

Exclusion Criteria:

• CNS involvement
• Known HIV positive
• T-cell lymphoma or history of indolent NHL
• Patients who will be treated with radiation therapy