This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.

Inclusion Criteria:

• Histological confirmation of hematological malignancies
• Acute leukemias
• Acute Myeloid Leukemia (AML) and related precursor neoplasms
• Favorable risk AML is defined as having one of the following:
• Acute lymphoblastic leukemia (ALL)/lymphoma
• Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features.
• Age 60 years of age or younger at the time of consent
• Karnofsky performance status ≥ 70% or Lansky play score 50% for ≤16 years of age.
• Adequate organ function

Exclusion Criteria:

• Pregnant or breastfeeding.
• Active uncontrolled infection within 1 week of starting preparative therapy
• Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR.
• Any prior autologous or allogeneic transplant
• CML blast crisis
• Active central nervous system malignancy

For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled:

• The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly.
• The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services.
• The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.