Poor prognosis dufuse large B-cell lymphoma (DLBCL) represents 50% of all DLBCL with overall cure rates ranging from 50-60% with modern dose-dense immunochemotherapy regimens such as R-CHOP14. Using an alternative strategy, as infusional and dose-adjusted R-EPOCH, the investigators have shown an 83% of complete responses (CR), with an estimated 5-year overall survival (OS) rate of 75% (García-Suárez et al. British Journal of Haematology 2007, 136:276). Despite this improvement in outcome, the search for new treatment strategies should continue. Therefore, compared with prior R-EPOCH the investigators decided to investigate whether the introduction of dexamethasone (40 mg IV on days 1-5) in place of prednisone (based upon data which demonstrated that the former was associated with enhanced Central Nervious System penetration) and the reduction of treatment intervals from 3 to 2 weeks would be feasible and might improve the outcome in this group of patients.

Medication, Dose and Method for Administration:

• Rituximab: 375 mg/m2, endovenous, according to the protocol of the service, day 1 (except in the first cycle, in which it will be on day 5).
• Etoposide: 50 mg/m2/day, in continuous 24-hour infusion, days 1 to 4.
• Adriamycin: 10 mg/m2/day, in continuous 24-hour infusion of, days 1 to 4.
• Vincristine: 0.4 mg/m2/day, in continuous 24-hour infusion, days 1 to 4
• Dexamethasone: 40 mg, endovenous, days 1 to 5. Followed by prednisone 30 mg (day +6), 20 mg (day +7), and 10 mg (day +8).
• Cyclophosphamide: 750 mg/m2, endovenous, in 30 minutes, day 5, after ending the continuous infusion of adriamycin, etoposide and vincristine.
• MESNA (If the dose of Cyclophosphamide is > 1 g/m2

Inclusion Criteria:

• Signing the Informed Consent.
• Histology: diffuse large B-cell lymphoma de novo (primary mediastinal B-cell lymphomas will be included provided that they have a mass greater than 7 cm in larger diameter) and follicular NHL grade 3b.
• aaIPI: 2-3.
• Age: Between 18 and 70 years.
• General Condition (ECOG/WHO): Proper organic function, defined by: FEVI ≥ 40%, serum creatinine < 150 µmol/L, serum bilirubin < 30 µmol/L, control of other medical conditions such as: infection, leukocytes ≥ 3.5 x 109/l and platelets ≥ 100 x 109/l (except if they are caused by lymphomatous infiltration of bone marrow or of the spleen).

Exclusion Criteria:

• HIV-positive.
• Pregnancy or breastfeeding.
• Serious disease compromising the performance of the therapeutic regimen.
• Recent history of another malignant disease (except skin cancer different from melanoma or carcinoma in-situ of the cervix), prior radiotherapy or chemotherapy, history of indolent lymphoma.
• CNS infiltration at diagnosis.