Preemptive CIML NK Cell Therapy After Hematopoietic Stem Cell Transplantation

Inclusion Criteria for Trial Enrollment: * Histologically or cytologically confirmed diagnosis of AML, MDS, or MDS/MPN that is at high risk for post-transplant relapse and that has measurable disease prior to transplant. Patients at high risk for post-transplant relapse include: * De novo AML diagnosed at or after age 60, except CBF AML * De novo AML in CR1 AND MRD+ by Hematologics Inc. flow cytometry pretransplant (this would be on the most recent pre-transplant bone marrow) * Secondary AML * AML with 5 - \> 10% blasts at the time of transplant who are judged by their treating clinician and study PI to have no benefit from additional pre-transplant chemotherapy * Any AML transplanted in CR2 or greater * TP53-mutated MDS or AML * Therapy-related MDS or AML * MDS with monosomy 7 * MDS with \>= 5% blasts at the time of transplant * MDS/MPN or CMML * Adequate organ function within 2 weeks of NK cell infusion as defined below (should correspond with admission for SCT): * Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease related hemolysis, then \< 3 x ULN) * AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN * Serum creatinine \</= 2.0mg/dL * O2 saturation: ≥90% on room air * LVEF \>40%. If there is no clinical evidence of a change in cardiovascular function from the time of pre-transplantation ECHO (per FACT standards should be performed within 6 weeks of stem cell infusion), then there is no need to repeat it. Otherwise, an ECHO will need to be repeated. * Adult patients (age ≥ 18) eligible for and planned to undergo a standard-of-care reduced intensity conditioning (RIC) HLA-matched related or related haploidentical allogeneic stem cell transplant using PTCY-based GVHD prophylaxis. All eligibility criteria and workups for undergoing SOC allogeneic SCT for the recipient and donor will be based on institutional standards and SOPs. * For patients with AML, the disease must meet criteria for CR/Cri according to 2017 ELN guidelines, or have 5-10% blasts at the time of the transplant and in the judgement of their primary BMT clinician and study PI to have no benefit from additional pre-transplant chemotherapy. For patients with MDS or MDS/MPN, the blast percentage on the bone marrow aspirate and biopsy must be less than 10%. * The same related donor is available to provide a non-mobilized apheresis product after the stem-cell donation. * ECOG performance status \<= 2 (Karnofsky \>= 60%, see Appendix C). * Negative pregnancy test for women of childbearing age * The effects of CIML NK cells combined with IL-2 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after IL-2 dose administration. * No laboratory evidence of ongoing hemolysis in opinion of investigator Exclusion Criteria Trial Enrollment: * Adult participants who are eligible for and who would be expected to have a greater benefit from myeloablative conditioning in their SOC allo HSCT as judged by their treating physician * Participants with mutations such as FLT3-ITD, IDH, or BCR-ABL mutations who are planned to receive targeted agent maintenance therapy to prevent relapse post-transplant are excluded. * Extramedullary leukemia involving sanctuary sites not readily accessible to immune surveillance, such as CNS or testis. Other sites of extramedullary relapse (e.g., leukemia cutis, granulocytic sarcoma) are acceptable. * The planned use of sirolimus for GVHD prophylaxis would result in exclusion of the patient from the study. Consideration of the addition of sirolimus to the GVHD prophylaxis regimen within the first 100 days after transplant must be reviewed with the study PI. * Prior history of allogeneic stem cell transplant other than SOC alloHSCT referred to in this study taking place 7 days prior to CIML NK infusion. * Prior history of solid organ (allograft) transplantation * Prior history of allergic reactions to cellular products * Uncontrolled concurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social illness that would limit compliance with study requirements. * Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and IL-2 and with the potential for teratogenic or abortifacient effects by Flu/Cy chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and IL-2, breastfeeding should be discontinued if the mother is treated on this study. * HIV-positive patients are excluded due to the potential for interaction between antiretroviral therapy as well as the risk for lethal infection in the context of marrow-suppressive therapy. * Patients with active and uncontrolled Hepatitis B or C are ineligible due to the high risk of treatment-related hepatotoxicity after cellular therapy. * Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1. History of other malignancy and have had complete remission of disease for at least 2 years; 2. Diagnosed and treated within the past 2 years for: nonmetastatic melanoma, surgically resected (not needing systemic chemotherapy) squamous cell carcinoma of skin and nonmetastatic prostate cancer not needing systemic chemotherapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study. 3. Diagnosed with MGUS or smoldering myeloma, and/or treated for multiple myeloma or plasmacytoma as long as attainment of complete remission by IMWG criteria following therapy. * Prior history of Grade 2 or higher hemolytic anemia (\>/= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause. Inclusion Criteria to Receive CIML NK Infusion * Adequate organ function within 24 hours of NK cell infusion as defined below: * Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN) * AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN * Grade ≥3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning (except for Grade 3 nausea, vomiting, diarrhea, or constipation). * No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with CIML NK infusion, (e.g., symptomatic congestive heart failure, unstable angina, cardiac arrhythmia) * No evidence of ongoing hemolysis in opinion of investigator Exclusion Criteria to Receive CIML NK Infusion: * Systemic steroid therapy (oral or IV) on the day of NK cell infusion * Uncontrolled concurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social illness that would limit compliance with study requirements. * Participants who have had other investigational agents within 4 weeks prior to CIML NK cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 8 weeks prior, or those who have not recovered from adverse events due to agents administered more than 4 weeks prior. Therapy with BCR-ABL inhibitors must be stopped at least 2 weeks before CIML NK cell infusion and may not be resumed during the DLT period. The use of tocilizumab for cytokine release syndrome after stem cell infusion does not exclude patients, but the use of steroids for the treatment of CRS excludes patients if they are still on steroids by the day of planned NK cell infusion. * Systemic steroid use of \>10mg/day of prednisone equivalent is an exclusion criteria unless there is a plan for dose to be tapered below this limit within 4 weeks prior to NK cell infusion. Patients must be off systemic steroid therapy on the day of planned NK cell infusion. -The presence of donor-specific antibodies (DSAs) with mean fluorescence intensity (MFI) \>1000 using a standard assay who do not receive a desensitization protocol prior to and during stem cell transplant, or else who do receive a desensitization protocol and have detectable DSAs +1 day after stem cell infusion. If inclusion/exclusion criteria are not met on planned day of CIML NK cell infusion, the NK cell infusion may be delayed for up to 48 hours to enable inclusion criteria to be met. However, patient may still receive CIML NK infusion if relevant parameters are reviewed and both PI and IND holder are in agreement with proceeding.