• CBC, platelet count, Creatinine, bilirubin, SGPT. [ Time Frame: CBC, platelet count 1-2 x weekly course 1, every 2-4 weeks while on therapy. Creatinine, bilirubin, SGPT weekly course 1, every 2-4 weeks while on therapy. ]
  

• Bone marrow aspiration to document remission then every 1-3 courses. Cytogenetics at remission if abnormal pretherapy. [ Time Frame: Bone marrow aspiration to document remission then every 1-3 courses. ]
  

Since decitabine is effective in MDS, we would like to continue investigating its activity, correlate methylation profiles with response, and improve on the efficacy: toxicity profile of the regimen. Preclinical studies indicate that longer exposure to decitabine is more active since the drug has to integrate into one, then the second DNA strand, before inducing the full hypomethylating effect. Therefore, an exposure of > 5 days (rather than the 3-day schedule used in MDS by Wijermans et al) may be better. On the other hand, it is yet unknown whether a longer exposure (10 days versus 5 days) would be clinically even more effective,and whether it would have more side-effects if the total dose of decitabine per course is the same. A subcutaneous decitabine schedule in MDS will also have multiple advantages (quality of life, less catheter-related infections, less hospital environment) in addition to possible better pharmacokinetic profile and better efficacy. The primary trial objective is to assess efficacy of the following decitabine regimens in high risk MDS:1) 10-day IV decitabine (D10), 2) 5-day IV decitabine (D5), 3) subcutaneous decitabine (DSQ). At the end of the trial, we will determine the probability that one of the combinations is superior to the others in terms of CR rate (see definitions, Section 10.0). We will also evaluate toxicity on each of the treatment arms. A maximum of 130 patients will be treated, at an expected accrual rate of 4.5 patients per month. If there is sufficient evidence that efficacy of one of the regimens is different from the others, the trial may be completed with a smaller number of patients. If there is sufficient evidence that efficacy of one of the regimens is different from the others, the trial may be completed with a smaller number of patients. As of April 2005, following accrual of 65 patients, the Bayesian design selected the 5 day IV schedule (decitabine 20 mg/m2 IV daily x 5) as probably the better one in relation to CR rat, the primary endpoint, as well as for incidences of myelosuppression and complications. The study will now continue with all new patients receiving the 5 day IV decitabine. For patients who are already on study, receiving the 5 day SQ or 10 day IV, the option to change to the 5 day IV will be offered to these patients who may elect to receive in subsequent courses, as this constitutes the new "standard" schedule on this particular study.

Inclusion Criteria:

• MDS and 5% or more marrow blasts, or IPSS risk intermediate 1-2 or high risk; or chronic myelomonocytic leukemia
• Performance status 0-2 (ECOG scale); adequate hepatic (bilirubin < 2 mg/dl) and renal functions (creatinine <2mg/dl); NYHA cardiac status III-IV excluded.
• Signed informed consent
• No prior intensive combination chemotherapy or high-dose ara-C (>/= 1g/m2 per dose). Prior biologic therapies, targeted therapies and single agent chemotherapy allowed.
• Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of Hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy.

Exclusion Criteria:

• Nursing and pregnant females are excluded. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients with active and uncontrolled infections
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements