The goal of this clinical research study is to compare how 2 different drugs, decitabine and azacitidine, when given on a shorter than standard dosing schedule, may help to control MDS. The safety of each study drug given on these schedules will also be studied.

This is an investigational study. Decitabine and azacitidine are both FDA approved and commercially available for use in patients with MDS. Giving these drugs on a different schedule than is standard is considered investigational.

The study doctor can tell you how the study drugs are designed to work.

Study Groups and Study Drug Administration:

Each cycle is approximately 28 days.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 4 groups:

• If you are in Group 1, you will receive decitabine by vein over about 1 hour on Days 1-3 of every cycle.
• If you are in Group 2, you will receive azacitidine either as an injection under your skin or by vein on Days 1-3 of every cycle.
• If you are in Group 3, you will receive azacitidine either as an injection under your skin or by vein on Days 1-5 of every cycle.
• If you are in Group 4, you will receive the standard of care. The study doctor can explain the treatment you will receive and the risks involved.

Transfusion-dependent participants will be randomly assigned to 1 of 3 groups

This is done because no one knows if one study group is better, the same, or worse than the other group. If you are among the first 20 participants, you will have an equal chance of being in any of the groups. If you enroll after that, you will have a higher chance of being assigned to the group that has had better results.

However, once you are assigned to a group, you will not be allowed to change groups.

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Study Visits:

One (1) time each month, blood (about 2 tablespoons) will be drawn for routine tests.

At the end of Cycle 2, then every 3 cycles for the first year, then every 6 cycles, you will have a bone marrow biopsy and/or aspirate to check the status of the disease and for cytogenetic testing.

After Cycle 1, if the study doctor decides it is acceptable, you may be allowed to receive treatment from your local cancer doctor. However, you must return to Houston at least every 3 cycles for study visits. How often these visits will occur will depend on what the doctor thinks is in your best interest.

Length of Study:

You may continue taking the study drug or standard therapy for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug or standard therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-Up:

When you are off-treatment, every 6 -12 months for up to 5 years, you will be called by a member of the study staff. You will be asked about any side effects you may be having. The phone calls will take about 5-10 minutes.

Inclusion Criteria:

1. Sign an IRB-approved informed consent document.
2. Age >/= 18 years.
3. IPSS low- or intermediate-1-risk MDS, including CMML-1
4. ECOG performance status of \