Inclusion Criteria:

• Patients must have histologically confirmed DLBCL with characteristic immunophenotypic profiles. Tumor tissue must be confirmed to express the CD20 antigen by flow cytometry or immunohistochemistry.
• Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
• Patient has not had any previous treatment.
• Stage II (not appropriate for abbreviated chemoimmunotherapy and radiotherapy), III or IV disease
• Able to adhere to the study visit schedule and other protocol requirements.

• Patients must have laboratory test results within these ranges:

  • Absolute neutrophil count > = 1500/mm³
  • Platelet count > = 75,000/mm³
  • Serum creatinine < = 1.5X upper limit of normal (ULN)
  • Total bilirubin < = 1.5X ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
  • AST (SGOT) and ALT (SGPT) < = 2 x ULN
• Disease free of prior malignancies for > = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
• Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. The effects of azacytidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Age >18 years.
• Ability to understand and the willingness to sign a written informed consent document.
• ECOG performance status of 0-2

Exclusion Criteria:

• Patients must not have any serious medical condition, laboratory abnormality,or psychiatric illness that would prevent the subject from signing the informed consent form.
• Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV or infectious hepatitis B.
• Known central nervous system involvement by lymphoma.
• Known or suspected hypersensitivity to azacitidine or mannitol.
• Patients must not have advanced malignant hepatic tumors.
• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.