Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma

Inclusion Criteria:

1. Age 18-60;

2. Histological confirmed diagnosis of Diffuse Large B-Cell Lymphoma CD20+ (newlydiagnosis or shifted from low grade NHL and not previously treated) or of FollicularLymphoma grade III according to REAL/WHO Classification.

3. Advanced stage II, stage III and stage IV with at least two aa-IPI risk factors.

4. Age-adjusted IPI 2-3.

5. ECOG performance status 0-2.

6. LVEF>45%, measured with echocardiography.

7. Normal hepatic, renal and pulmonary functions.

8. HIV, HCV and HBV negativity.

9. HCV+ admitted only in histologically confirmed absence of replication marks.

10. Positive serology for HBV (occult carriers: AntiHBcAg+, HbsAg-, AntiHBsAg+/-) admittedonly upon negativity of weakly positive HBV-DNA test.

11. Life expectancy > 3 months.

12. Negative pregnancy test.

13. Written Informed Consent.

Exclusion Criteria:

1. Histological diagnosis of:

• Lymphoblastic NHL

• Burkitt's Lymphoma

• CD 20 negative B-cell Lymphoma

• grade I-IIIa Follicular Lymphoma

• Mantle Cell Lymphoma

• Primary mediastinal NHL with exclusively intrathoracic localization.

2. Age > 60

3. Stage I disease

4. Age-adjusted IPI 0-1

5. ECOG-PS>3, if not related to Lymphoma

6. Renal impairment (creatinine>1,2 mg/dl or creatinine clearance < 60ml/min)

7. Hepatic impairment (AST/ALT or bilirubin > 2,5 times normal limit, unless due toLymphoma)

8. HIV positive patients and/or with HBV or HCV active infection(documented by HBV-DNAand HCV-RNA positive tests)

9. Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension (resting diastolic blood pressure > 115 mmHG), uncontrolled multifocal cardiacarrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA classIII-IV

10. LFEV<45%

11. Severe diabetes mellitus difficult to control with adequate insulin therapy

12. Severe chronic obstructive pulmonary disease with hypoxemia

13. Active bacterial, viral of fungal infection requiring systemic therapy

14. Concurrent thrombohemolytic disease

15. HIV positivity

16. HBV positivity

17. Positive serology for HBV (occult carriers: AntiHBc+, HbsAg-, AntiHbs+/-) withpositive HBV-DNA test

18. HCV positivity in presence of replication marks (HCV+, CRP+, AST 1,5-2 times normalranges)

19. CNS localization of disease

20. Prior (during last 3 years) or concurrent malignancy except adequately treated basalcell carcinoma of the skin or carcinoma in situ of the cervix or early stage prostatecancer not requiring systemic therapy, or early breast cancer treated with surgeryalone. Any other co.existing medical condition that would preclude study therapyadministration

21. Pregnancy or breast-feeding women

22. Inability of the patient to give her/his informed consent

23. Known hypersensitivity or anaphylactic reaction to murine antibodies or proteins