Inclusion Criteria:
* Participants must have pathologically confirmed AML in CR1 as defined by:
* Bone marrow biopsy with \< 5% blasts
* No clusters or collections of blast cells
* No extramedullary leukemia
* Absolute neutrophil count ≥ 1000/µL (achieved post-induction at some point)
* Please note that full platelet recovery is not necessary, and thus, patients achieving CRp are eligible.
---Or participants have pathologically confirmed MDS as defined by:
* Bone marrow biopsy with \<10% blasts
* Patients receiving MDS-directed therapy must be off treatment for \> 2 weeks prior to start of conditioning.
* Participants must be designated to undergo reduced intensity allogeneic peripheral blood hematopoietic stem cell transplantation (HCT). Consent will be obtained prior to admission for HCT. The following HCT conditions must be planned:
* Donors must be 8/8 HLA-matched (at the allele level) as defined by matching at HLA-A, -B, -DR and -C who pass institutional standard to serve as a peripheral blood stem cell donor
* Donor grafts must be G-CSF mobilized peripheral blood stem cells with dose and apheresis logistics at the discretion of institutional standard
* Conditioning therapy will be one of the following 3 options:
* Fludarabine / Melphalan where fludarabine is ≥ 90 mg/m2 IV total dose and melphalan is 100-140 mg/m2 IV total dose. Exact logistics of administration are at the discretion of institutional standard.
* Fludarabine / Busulfan where fludarabine is ≥ 90 mg/m2 IV total dose and busulfan = 6.4 mg/kg IV total dose. Exact logistics of administration are at the discretion of institutional standard.
* Fludarabine / Busulfan where fludarabine is ≥ 90 mg/m2 IV total dose and busulfan is dosed to achieve AUC of 4000 µmol/min based on a pharmacokinetics determined from a test dose. Exact logistics are at the discretion of institutional standard.
* GVHD prophylaxis is comprised of tacrolimus / short course methotrexate as defined by tacrolimus started prior to day 0 of HCT and methotrexate given after HCT on days +1, +3 and +6 ± +11 at a dose of 5-10 mg/m2 IV. Exact logistics are at the discretion of the treating institution.
* Age ≥ 60 and ≤ 80 years old
* ECOG performance status 0-2
* Male participants must agree to use an acceptable method for contraception during the entire study treatment period and through 6 months after the last dose of treatment.
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Have had a prior allogeneic HSCT.
* Patients without normal organ function defined as follows:
* AST (SGOT), ALT (SGPT) and Alkaline Phosphatase \>3 × institutional Upper Limit of Normal (ULN)
* Direct bilirubin \>2.0 mg/dL
* Adequate renal function as defined by calculated creatinine clearance ≤ 40 mL/min (Cockcroft-Gault formula)
* Have a history of other malignancy(ies) unless:
* They have been disease-free for at least 5 years and are deemed by the treating investigator to be at low risk for recurrence of that malignancy,
\--- or
* The only cancer they have had is cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin
* Have a chronic or active infection that requires systemic antibiotics, antifungal or antiviral treatment.
* Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 40%, as measured by MUGA scan or echocardiogram)
* Have an uncontrolled intercurrent illness including, but not limited to, ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Have active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
* Be HIV-positive
* Have a systemic infection requiring IV antibiotic therapy, nor any other severe infection
* Planned use of ex vivo or in vivo T-cell depletion
* Have current or a history of ventricular or life-threatening arrhythmias or diagnosis
