Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

Inclusion Criteria: * Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR composite lymphoma with \>= 50% DLBCL * Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis * Karnofsky Performance Status \>= 70 (ECOG 0, 1) * No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense), immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is allowed only if required for maintenance of another chronic disease (e.g., rheumatoid arthritis) * Patients aged \>= 60 years, or patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction \>= 0.45 (45%) by MUGA or echocardiography, performed within two months of study entry * Patients must be willing to give written informed consent, and sign an institutionally approved consent form prior to initiating genasense or any study related activities (i.e., Genasense \& microarray) * Females of childbearing potential must have a negative serum pregnancy test prior to enrollment in the study * Adequate venous access for 7-day continuous infusion * Patients without evidence of severe organ dysfunction as determined within two weeks of 1st cycle of CHOP-R: 1) Hemoglobin \> 8 g/dl; 2) Absolute neutrophil count \> 1000/; 3) Platelets \> 100,000 (lower blood counts may be acceptable if due to lymphoma after review with principal investigator); 4) Creatinine =\< 2.0 mg/dL (unless due to NHL); 5) Bilirubin =\< 2.0 mg/dL; 6) AST =\< 3 x upper normal; 7) ALP =\< 3 x upper normal (unless due to NHL) * Men and women of reproductive potential must agree to use TWO of the following forms of birth control every time they have sex throughout the study and for up to 3 months following discontinuation of study drug: hormonal birth control methods, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicidal, IUD, or surgical sterilization while participating in this study Exclusion Criteria: * Significant medical disease other than cancer including: 1) Any bleeding or coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled seizure disorder; and 6) Active infections * Less than 3 weeks from prior major surgery * Prior organ allograft * Known HIV infection (due to expected frequent occurrence of myelo-suppression and immunosuppression) * Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding (women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment or remain abstinent) * Women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment (unless the subject or subject's partner(s) is sterile, i.e., women who have had a hysterectomy or have been post-menopausal for at least twelve consecutive months) or remain abstinent * Known hypersensitivity to phosphorothiate-containing oligonucleotides * Concurrent investigational, corticosteroid therapy or any other anti-cancer treatments (such as chemotherapy, radiation, biologic or investigational therapies) while receiving protocol therapy; other than one cycle CHOP-R allowed based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense; other than chronic steroid use for another indication (For stage I/II or as clinically indicated- involved field irradiation as per standard practice is accepted) * Other investigational drug therapy within 30 days of study entry * Secondary leukemia or history of antecedent hematologic disorder * History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three or more years) * No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma * Concomitant anticoagulant therapy is not permitted (with the exception of 1 mg/day of warfarin for central line prophylaxis) * Known hypersensitivity to G3139 (Genasense) or R-CHOP * Neurologic disorders, overt psychosis, mental disability or evidence of limited capacity to provide fully informed consent or cooperation with the complexities of the treatment program