Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

Inclusion Criteria: 1. Age 18-75 2. Diagnosis of CD20+ B-diffuse large cell de novo or transformed or follicular lymphoma grade IIIb 3. Stage II, III, IV according to Ann Arbor criteria 4. Chemoresistant disease after first line treatment (CHOP-like + Rituximab) or relapsed patients after one or two lines of chemotherapy not-eligible for high dose chemotherapy and autologous stem cell transplantation 5. Performance status 0-2 according to WHO criteria 6. HIV negativity 7. Normal liver, lung and kidney function: conjugated bilirubin up to 2 x ULN, alkaline phosphatase and transaminases up to 2 x ULN, creatinine clearances ≥45 ml/min 8. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 150 x 109/l and bone marrow involvement \< 25% before first Zevalin infusion. 9. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 100 x 109/l before second Zevalin infusion 10. Use of effective contraception for the entire treatment period in patients sexually active 11. Negative pregnancy test in child bearing potential women 12. Life expectancy \> 6 months 13. Written informed consent Exclusion Criteria: 1. More than two lines of prior chemotherapy before study entry 2. Prior high dose chemotherapy and autologous stem cell transplantation 3. HIV positivity 4. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative 5. HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed 6. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances 7. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug 8. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis 9. Pregnant or breastfeeding 10. CNS lymphoma involvement. 11. History of malignant carcinoma within the last 3 years other than squamous cell and basal cell carcinoma. 12. Cardiac failure with VEF \< 40% 13. Clinical evidence of not controlled infections