Haploidentical Stem Cell Transplant with Umbilical Cord Blood Transplant for the Treatment of Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome

Inclusion Criteria

• Patients with the following hematologic malignancies: * Acute myelogenous leukemia (AML): High-risk AML including: ** Antecedent hematological disease (e.g., myelodysplasia [MDS]) ** Treatment-related ** Complete remission (CR1) with poor or intermediate-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, TP53 mutations, complex cytogenetics) ** Patient must be in complete remission (CR)1, CR2, CR3 or complete response with incomplete bone marrow recovery (CRi) * Acute lymphoblastic leukemia (ALL) ** High-risk CR1 including: *** Poor-risk cytogenetics (e.g., t[9;22] or 11q23 rearrangements) *** Presence of minimal disease by flow cytometry or polymerase chain reaction (PCR) or Clonoseq after 2 or more cycles of chemotherapy *** No CR within 4 weeks of initial treatment ** Patient must be in CR1, CR2, CR3, or CRi * Myelodysplastic syndromes (MDS), intermediate, high or very high risk by the revised international prognostic scoring system (IPSS-R) or treatment related MDS
• Age ≥ 18 years
• Patients without a suitable human leukocyte antigen (HLA)-matched related or unrelated donor
• Patient with the following suitable grafts: * A 4-8/8 HLA high resolution matched cord blood unit with a cell dose of 1.0 x 10^5 CD34 cells/kg * A haplo-identical donor with a goal cell dose of >= 4.0 x 10^6 CD34cells/kg (minimum 2 x 10^6 CD34 cells/kg)
• Concurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients with inadequate organ function as defined by: * Creatinine clearance < 40ml/min (Cockcroft-Gault) * Bilirubin >= 2 X institutional upper limit of normal unless Gilbert syndrome * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) >= 3 X institutional upper limit of normal * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 3 X institutional upper limit of normal * Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCOc) < 60% * Cardiac: left ventricular ejection fraction < 40% * Karnofsky performance status (KPS) < 70
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with conditioning have the significant potential for teratogenic or abortifacient effects
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
• Prior autologous stem cell transplant or chimeric antigen receptor T cell (CAR-T) within the preceding 6 months or prior allogeneic transplant