<p>Key Inclusion Criteria:</p>
<ol>
<li>
<p>Age at the time of enrollment:</p>
<ol>
<li>For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age &ge; 12 and &le; 78 years</li>
<li>For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age &ge; 12 and &le; 65 years</li>
</ol>
</li>
<li>Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or very high risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with &le; 10 percent of blast cells in bone marrow (BM)</li>
<li>Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)</li>
<li>Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor</li>
<li>Estimated glomerular filtration rate (eGFR) &gt; 50 mL/minute (MAC with tacrolimus) or &gt; 30 mL/minute (NMA/RIC or MAC without tacrolimus)</li>
<li>Cardiac parameters: Cardiac ejection fraction &ge; 45 percent (MAC) or &ge; 40 percent (NMA/RIC)</li>
<li>Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) &ge; 50 percent for MAC or &ge; 40 percent for NMA/RIC</li>
<li>Liver function: Total bilirubin &lt; 1.5 times upper limit of normal (ULN) (MAC) or &lt; 3 times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) &lt; 3 times ULN (MAC) or &lt; 5 times ULN (NMA/RIC)</li>
<li>Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)</li>
</ol>
<p>Key Exclusion Criteria:</p>
<ol>
<li>Prior alloHCT</li>
<li>Currently receiving corticosteroids or other immunosuppressive therapy except for approved disease-specific therapy for the patient's underlying hematologic malignancy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed</li>
<li>Planned donor lymphocyte infusion (DLI)</li>
<li>Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab</li>
<li>Positive anti-donor HLA antibodies against a mismatched allele in the selected donor</li>
<li>Low performance score: For MAC: Karnofsky Performance Score (KPS) &lt; 70 percent, For NMA/RIC: &lt;60 percent</li>
<li>High HCT-specific Comorbidity Index (HCT-CI): For MAC &gt; 4, For NMA/RIC &gt;6</li>
<li>Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment</li>
<li>Seropositive for human immunodeficiency virus (HIV)-1 or -2, human T-lymphotropic virus (HTLV)-1 or -2 or Hepatitis B surface antigen (HbsAg) or anti-Hepatitis C virus (HCV) antibody (Ab)</li>
<li>Any uncontrolled autoimmune disease requiring active immunosuppressive treatment</li>
<li>Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected. Patients with concurrent indolent hematologic malignancies that do not require active treatment and are under active surveillance only (such as CLL, low-grade lymphomas, smoldering MM, MZL) may be included with the approval of Medical Monitor</li>
<li>History of idiopathic or secondary myelofibrosis</li>
<li>Women who are pregnant or breastfeeding</li>
</ol>