Venetoclax in Combination With Azacitidine (VEN/AZA) Followed by Donor Lymphocyte Infusion (DLI) for Patients With Very High-Risk Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)

Eligibility Criteria

• 1. Male and female patients between the ages of 18-75.
• 2. Patients with a histologic diagnosis of AML in morphological remission (\<5% bone marrow (BM) blasts) prior to allogeneic hematopoietic cell transplantation and very high-risk for relapse defined as: (i) Presence of measurable residual disease (MRD) by multicolor flow cytometry (MFC) prior to transplant and receiving a reduced intensity conditioning (RIC) or nonmyeloablative (NMA) regimen (ii) Presence of MRD by MFC at day +30 post-transplant (iii) All patients with monosomal karyotype (MK) and those with 17p/tumor protein p53 (TP53) mutated disease irrespective of MRD status and intensity of conditioning regimen.
• 3. Adequate hematopoietic recovery after HCT, defined as:
• * Absolute neutrophil count (ANC) \>= 1 x 10\^9/L without daily use of myeloid growth factors
• * Platelet count \>= 50 x 10\^9/L without platelet transfusion within 1 week
• 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• 5. Serum creatinine =\< 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min
• 6. Serum bilirubin =\< 1.5 x upper limit of normal (ULN)
• 7. Aspartate transaminase (AST) or alanine transaminase (ALT) =\< 2.5 x ULN
• 8. Alkaline phosphatase =\< 2.5 x UL
• 9. Negative serum or urine pregnancy test for women with reproductive potential.
• 10. A negative donor-specific antibody (DSA) assay (i.e., Micro-Flow Imaging (MFI) \<m3000) for recipients of any mismatched graft (including haploidentical) HCT.
• 1. Active disease (\>5% blasts or any evidence of extra-medullary disease) at the time of transplantation or at day +30
• 2. Active acute graft-versus-host disease (aGVHD) requiring systemic IST or history of aGVHD grade III or higher.
• 3. Active chronic GVHD requiring systemic immunosuppressive therapy (IST).
• 4. Active uncontrolled systemic fungal, bacterial, or viral infection
• 5. Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
• 6. Significant active cardiac disease within the previous 6 months, including: New York Heart Association (NYHA) class III or IV congestive heart failure. Unstable angina, angina requiring surgical or medical intervention, and/or myocardial infarction.
• 7. History of any other malignancy within 2 years prior to study entry, except for: adequately treated in situ carcinoma of the cervix or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; myelodysplastic syndrome.