This clinical trial studies potential genetic markers which might be used to predict which patients with acute myeloid leukemia or myelodysplastic syndromes respond to decitabine. This study will contribute to the efforts to find effective and less toxic therapies to provide durable remissions in a significant proportion of elderly AML patients.

Inclusion Criteria:

All of the following:

• Patient must have non-M3 AML or MDS

• An adverse risk karyotype defined by:

  • Complex karyotype by cytogenetics, or
  • Deletion of all or part of chromosome 5, 7, 12, or 17 defined by FISH or cytogenetics, or
  • Somatic TP53 mutation

All of the following:

1. Patient must have an ECOG performance status ≤ 2.

2. Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics.

3. Patient must have peripheral white blood cell count < 50,000/mcl.

4. Patient must have adequate organ function, defined as:

   1. Total bilirubin < 1.5 x ULN
   2. AST/ALT < 2.5 x ULN
   3. Serum creatinine < 2.0 x ULN

5. Patient must have undergone ≤ 2 cycles of prior hypomethylating agent (decitabine or azacitidine).

6. Patient must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").

7. Patient must be > 18 years of age.

8. Patient must be able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

• Patient must not be pregnant or nursing
• Patient must not have acute promyelocytic leukemia or t(15;17) observed by FISH.
• Patient must not have known central nervous system (CNS) leukemia
• Patient must not have a history of positive human immunodeficiency virus (HIV) serology
• Patient must not have a history of positive hepatitis C serology
• Patient must not have undergone prior allogeneic stem cell transplant
• Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, ongoing or active graft-versus-host disease (GVHD), congestive heart failure of New York Heart Association (NYHA) class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
• Patient must not have had radiation therapy within 14 days of enrollment
• Patient must not have received any chemotherapy within 21 days of enrollment and any acute treatment-related toxicities must have returned to baseline. Patients may be receiving hydrea at time of enrollment.

-Adverse events were collected from the start of treatment until 30 days following the last day of study treatment (average 5 months) -All deaths were collected from enrollment through study completion date.

Grades 1-5 adverse events will be recorded for the first 50 enrolled participants. Grades 3-5 will be recorded for the remainder of enrolled participants (n=64).