The goal of this clinical research study is to compare how two different drugs, decitabine and azacitidine, when given on a shorter than standard dosing schedule can help to control MDS. The safety of the drugs will also be studied.

Decitabine is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.

Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better. This could cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

• If you are in Group 1, you will receive decitabine by vein over about 1 hour.
• If you are in Group 2, you will receive azacitidine either as an injection under your skin or through a vein. If by vein, the infusion will take about an hour.

At first, there will be an equal chance of being assigned to either group. However, as the study goes on and more information becomes available, the chance of being assigned to the group that has shown the most effectiveness will increase. However, once you are already enrolled and assigned to a group, you will not be eligible to change groups.

Study Drug Administration:

Each cycle is 28 days.

You will receive the study drug on Days 1-3 of every cycle and you will receive at least 2 cycles of study drug.

Study Visits:

Every 7-14 days, blood (about 2 tablespoons) will be drawn for routine tests.

At the end of Cycle 2, you will have a bone marrow biopsy and/or aspirate to check the status of the disease. This will then be repeated every 2-4 cycles until any point that the disease appears to have responded to the study drug, then as often as the study doctor thinks is necessary. To collect a bone marrow biopsy/aspirate, an area of the hip bone is numbed with anesthetic, and a small amount of bone and/or bone marrow is withdrawn through a large needle.

After Cycle 3:

If the study doctor decides it is acceptable, you may be allowed to receive treatment from your local cancer doctor. However, you have to return to Houston at least every 3 months for your study visits.

The frequency of the visits will depend on what the doctor thinks is in your best interest.

Length of Study:

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

Follow-Up Visits:

One (1) time every 3 months after your last dose of study drug, you will return to the clinic for a bone marrow aspiration to check the status of the disease.

Other Information:

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.

This is an investigational study. Decitabine and Azacitidine are both FDA approved and commercially available for use in patients with MDS.

Up to 120 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Sign an Institutional Review Board (IRB)-approved informed consent document.
2. Age >/= than18 years
3. de novo or secondary International Prostate Symptom Score (IPSS) low- or intermediate-1 - risk MDS, including CMML
4. Eastern Cooperative Oncology Group (ECOG) performance status of \

3 years, 3 months