Venetoclax and Azacitidine for the Treatment of High-Risk Recurrent or Refractory Myelodysplastic Syndrome

Inclusion Criteria: * For phase I, patients can be HMA-naive high-risk MDS (Int-2 or high risk by the International Prognostic Scoring System \[IPSS\] with overall score \>= 1.5) with excess blasts \> 5%, or relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with \> 5% blasts * For phase II, patients will be divided into 2 cohorts: Cohort A: patients with HMA-naive high-risk MDS (Int-2 or high risk by the IPSS with overall score \>= 1.5) with excess blasts \> 5%. Cohort B: patients with relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with \> 5% blasts are eligible. Note: Patients with chronic myelomonocytic leukemia (CMML) and therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =\< 10,000/ul prior to initiation of venetoclax * Total bilirubin \< 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement * Alanine aminotransferase (ALT) \< 4 x ULN unless considered due to leukemic involvement * Creatinine \< 2 x ULN unless related to the disease * Signed written informed consent. Consent may be translated for Non-English Speaking Patients per institutional policy. * Females mu…