A Study of Engineered Donor Grafts (TregGraft) for Allogeneic Transplantation for Hematologic Malignancies (blood cancer)

Open to people ages 18-65

Recipients must meet all of the following criteria:

1. Patients must diagnosed with one of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:
2. acute myeloid, lymphoid or mixed phenotype leukemia
3. high or very high risk myelodysplastic syndromes
4. Patients with active acute leukemia (i.e. not in morphologic complete response) must have bone marrow infiltration by leukemic blasts of <= 10%,
5. Patients must be matched to a related or unrelated donor
6. Estimated glomerular filtration rate (eGFR) > 50 mL/minute
7. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
8. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
9. Total bilirubin < 2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded) and ALT/AST < 3 times ULN

Recipients meeting any of the following exclusion criteria will not be eligible:

1. History of prior allogeneic HCT
2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
3. Pre-planned donor lymphocyte infusion (DLI)
4. Planned pharmaceutical in vivo or ex vivo T cell depletion
5. Positive for anti-donor HLA antibodies against an allele in the selected donor
6. Karnofsky performance score < 70%
7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
10. . Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
11. . Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
12. . Women who are pregnant or breastfeeding