• determine the effect of azacitidine + best supportive care (BSC), relative to conventional care regimens + BSC, on hematologic status & status according to International Working Group (IWG) criteria & episodes of infections requiring IV antibiotics; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• determine the time to relapse after CR or PR, or disease progression (according to IWG criteria), in MDS patients treated with azacitidine + BSC, as compared with patients receiving conventional care regimens + BSC; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• to determine the time to transformation to AML, in MDS patients treated with azacitidine plus best supportive care, as compared with patients receiving conventional care regimens plus best supportive care; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• to determine the effect of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care on time to AML transformation or death from any cause; [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• to determine the safety and toxicity of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care in MDS patients. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

• determine the effect of azacitidine + best supportive care (BSC), relative to conventional care regimens + BSC, on hematologic status & status according to International Working Group (IWG) criteria & episodes of infections requiring IV antibiotics;
• determine the time to relapse after CR or PR, or disease progression (according to IWG criteria), in MDS patients treated with azacitidine + BSC, as compared with patients receiving conventional care regimens + BSC;
• to determine the time to transformation to AML, in MDS patients treated with azacitidine plus best supportive care, as compared with patients receiving conventional care regimens plus best supportive care;
• to determine the effect of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care on time to AML transformation or death from any cause;
• to determine the safety and toxicity of azacitidine plus best supportive care, relative to that of conventional care regimens plus best supportive care in MDS patients.

The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled.

Comparison/Control Interventions: Best supportive care, or low dose cytarabine plus best supportive care.

Duration of Intervention: Patients will be treated until death, withdrawal, or conclusion of the study.

• Drug: Azacitidine
• Other: Physician Choice

• Experimental: Study Drug
• Active Comparator: Physician choice of low dose cytarabine, standard chemotherapy or best supportive care consisting of blood products, growth factors, antibiotics

Inclusion Criteria:

• Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for MDS and a relatively high risk of AML transformation, with an International Prognostic Scoring System score of INT-2 or High.
• Be 18 years of age or older
• Have a life expectancy of at least 3 months
• Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
• Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
• Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
• Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal

Exclusion Criteria:

• Secondary MDS
• Prior treatment with azacitidine;
• Prior history of AML;
• Malignant disease diagnosed within prior 12 months;
• Metastatic disease;
• Hepatic tumors;
• Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
• Prior transplantation or cytotoxic therapy to treat MDS;
• Serious medical illness likely to limit survival to 12 months or less;
• Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
• Active HIV, viral hepatitis type B or C;
• Treatment with investigational drugs during prior 30 days.