PRIMARY OBJECTIVES: I. To assess the feasibility and determine the rate of rapid turn around, that is within 7 working days of receipt of adequate tissue at UNMC for a AFFYmetrix microarray study of newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) who will then receive treatment on this protocol. II. To evaluate efficacy (complete response rate) of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) to newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling or IHC as compared to newly diagnosed patients with DLBCL who do not express the ABC type that go on to receive standard CHOP-R (control). III. To evaluate the toxicity of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) for newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling. OUTLINE: Patients with diffuse large B-cell lymphoma (DLBCL) that expresses ABC type proceed to treatment in group I. Patients with DLBCL that does not express ABC type proceed to treatment in group II. GROUP I (oblimersen sodium and standard CHOP-R): Patients receive oblimersen sodium IV continuously on days 1-7. Patients also receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 5 and prednisone orally on days 5-10. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. GROUP II (standard CHOP-R alone): Patients receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and prednisone orally on days 1-5. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.