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