Safety and Efficacy of Allogeneic NK Cell Infusions in Patients With Relapsed/Refractory AML and High Risk MDS

Inclusion Criteria: 1. Patients ≥ 18 years of age and weighing at least 40 kg, inclusive, with persistence or relapse/progression of AML, MDS, or MDS/MPN overlap (within 28 days of enrollment) and: 1. a diagnosis of persistence or relapse/progression of AML and ≥ 5% blasts in the marrow or blood following at least 1 cycle of induction therapy, or 2. a diagnosis of intermediate, high, or very high-risk MDS according to IPSS-R classification (Greenberg et al., 2012) who are resistant or refractory to at least one course of therapy including demethylating agents (having had at least 4 cycles) with ≥ 5% blasts in the marrow or blood, or 3. a diagnosis of overlap of an MPN with MDS features and also are resistant or refractory to at least one course of therapy including demethylating agents (having had at least 4 cycles) with ≥ 5% blasts in the marrow or blood. 2. Written informed consent in accordance with federal, local, and institutional guidelines. 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Meet the following laboratory criteria within 7 days of enrollment: 1. ALT/SGPT and AST/SGOT \< 3x the upper limit of normal (ULN) unless due to underlying disease state 2. Calculated creatinine clearance ≥ 45.0 mL/min as estimated by Cockcroft Gault and dialysis independent (Cockcroft et al., 1976) 3. Total bilirubin ≤ 2.0 mg/dL (Patients with Gilbert's or Meulengracht Syndrome must have a total bilirubin \< 5.0 mg/dL). 6. Females cannot be pregnant or breast-feeding from time of enrollment or for 3 months post final infusion. 7. Women of childbearing potential is willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of protocol-specified therapy. Men who have a female partner of childbearing potential are together willing to use 2 highly effective forms of contraception for at least an additional 3 months after the last dose of protocol- specified therapy. 8. Patients status post allogeneic BMT or other donor lymphocyte infusions are eligible, but they must be at least 60 days from the last infusion of cell therapy products. 9. Patients must have other anti-leukemia therapies stopped 2 weeks prior to infusion on this study. Hydroxyurea and/or pheresis ARE allowed prior to this study until 1 day prior to infusion. Exclusion Criteria: 1. Weight less than 40 kg. 2. Patients with progressive infections at time of first infusion (patients with treated infections documented as controlled by the treating team are eligible). 3. Patients with history of active seizure disorder (having a documented seizure within the prior year) or any autoimmune disease with CNS involvement. 4. Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and any targeted small molecules or biologics), or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1. 5. Patients with proven, progressive severe autoimmune disease such as multiple sclerosis, active Guillain Barré syndrome, poliomyelitis, Sjogren's are not eligible. Given the immediate, life threatening nature of the relapsed cancer in this patient population, those with other stable and non-immediate non-threatening autoimmune disorders (such as thyroid disease or diabetes and others) are eligible. 6. Diagnosis of any other malignancy within 3 years, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention other than hormonal therapy, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms. 7. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. 8. Any active acute Graft-versus-Host Disease (GvHD) \> Grade 1 overall or systemic treatment of more than 10 mg prednisone daily (or equivalent); patients must have been off any calcineurin inhibitors for at least 28 days prior to starting therapy on this study. 9. Current use of immunosuppressive medications at the time of study enrollment and within 2 weeks of any study treatments, except: 1. Intranasal, inhaled, topical steroids, or local steroid injection 2. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent 3. Steroids as premedication for hypersensitivity reactions at physiologic doses ≤ 10 mg/day of prednisone or equivalent