Inclusion Criteria

Inclusion criteria

1. Histologically confirmed CD20 positive Diffuse Large B-cell Lymphoma (DLBCL)

2. Advanced stage: stage III, IV and/or bulky disease (largest diameter ≥ 10.0 cm)
regardless of stage

3. Previously untreated.

4. Performance status: ECOG 0-2.

5. Age ≥ 18

6. At least one or more bidimensionally measurable lesion(s)

- ≥ 2 cm by conventional CT

- ≥ 1 cm by spiral CT

- skin lesion (photographs should be taken) ≥ 2 cm

- measurable lesion by physical examination ≥ 2 cm

7. Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically
significant abnormalities

8. Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L)

9. Adequate liver functions:

- Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of
DLBCL involvement of the liver)

- Bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of DLBCL
involvement of the liver)

10. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC)
≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone
marrow involvement by lymphoma

11. Life expectancy ≥ 6 months

12. A negative serum or urine pregnancy test prior to treatment must be available both
for pre menopausal women and for women who are < 1 years after the onset of
menopause.

13. Informed consent

Exclusion criteria

1. Other subtypes NHL than DLBCL

2. Patients who transformed follicular lymphoma or other indolent lymphoma

3. Primary Central Nervous System (CNS) DLBCL;

4. CNS involvement by lymphoma or any evidence of spinal cord compression. Brain CT/MRI
is only mandatory (within 4 weeks) in case of clinical suspicion of CNS involvement
by lymphoma. Patients who have only had prophylactic intrathecal chemotherapy against
CNS disease are eligible.

5. Patients with a known history of HIV seropositivity or HCV (+). Patients who have HBV
(+) are eligible. However, primary prophylaxis using antiviral agents (i.e.
lamivudine) is recommended for HBV carrier to prevent HBV reactivation during whole
treatment period.

6. Any other malignancies within the past 5 years except curatively treated non-melanoma
skin cancer or in situ carcinoma of cervix uteri

7. Pregnant or lactating women, women of childbearing potential not employing adequate
contraception

8. Other serious illness or medical conditions

- Unstable cardiac disease despite treatment, myocardial infarction within 6
months prior to study entry

- History of significant neurological or psychiatric disorders including dementia
or seizures

- Active uncontrolled infection (viral, bacterial or fungal infection)

- Other serious medical illnesses

9. Known hypersensitivity to any of the study drugs or its ingredients (i.e.,
hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human
antibodies)

10. Concomitant administration of any other experimental drug under investigation, or
concomitant chemotherapy, hormonal therapy, or immunotherapy.