The study is planned to compare the outcome of aggressive NHL patients in partial remission after four courses of front-line therapy, randomly assigned to receive either additional four courses of the same regimen or a modified HDS program.

Inclusion Criteria:

• Newly diagnosed, untreated patients with histologically documented aggressive lymphoma;
• Age between 18 and 65 years;
• Clinical stage at diagnosis: I A bulky - IV B;
• Reduction of tumoral masses, after four courses of induction therapy, between 50 and 75%;
• Serum negativity for HIV, HbsAg and HCV;
• ECOG performance status 0 through 4;
• Adequate bone marrow function;
• Adequate renal and hepatic functions;
• Left ventricular ejection fraction (LVEF) > 50%;
• No previous malignant disease;
• No previous chemo-radiotherapy;
• No cerebral or CNS involvement, assessed by clinical history, physical examination and CSF examination through lumbar puncture;
• Written informed consent given at time of randomization.

Exclusion Criteria:

• Clinical stage I no bulky, or CS IIA-B with less than three sites of disease involved;
• Patients with CR, unconfirmed complete remission (uCR), very good PR (>75%) and clinical response less than 50%, as defined by Cheson et al., following four courses of induction therapy;
• Tumor involvement of CNS (except patients with peridural masses without liquor involvement , who can be enrolled in this study);
• Indolent lymphoma transformed in more aggressive histologic type, even if never previously treated;
• Aggressive non-Hodgkin's lymphoma in pre-transplanted patient;
• Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension, (resting diastolic blood pressure > 115 mmHg), uncontrolled multifocal cardiac arrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA class III-IV;
• Left ventricular ejection fraction (LVEF) < 50%;
• Evidence of any severe active acute or chronic infection;
• Concurrent malignancy of history of other malignancy, except basal cell carcinoma of the skin (BCC) and in situ cervical carcinoma (CIN);
• myelodisplastic syndrome;
• HbsAg, HIV-positive, or HCV-RNA-positive patients;
• Patient with psychiatric, or any disorder that compromises ability to give truly informed consent for participation in this study;
• Pregnant woman; potential child-bearing women can be enrolled if adequate contraceptive precautions are used before entering this trial and for the duration of the trial;
• Concerns for patient's compliance with the protocol procedures.