The Rapid Study: Randomized Phase II Study To Expedite Allogeneic Transplant With Immediate Haploidentical Plus Unrelated Cord Donor Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients

Inclusion Criteria for Search Phase: 1. Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by international prognostic scoring system revised for whom transplant is recommended 2. 18 years of age or older 3. Subject is likely to be considered for allogeneic transplant in the opinion of the transplant physician (based on age of patient, health, cytogenetics, and/or molecular characteristics). 4. Karnofsky Performance Status (KPS) \>/= 70% at time of enrollment. An exception will be made for those with lower KPS at enrollment with an acute worsening that is likely to resolve in the treating physicians judgment (e.g., reversible infection,trauma, medication reaction, etc) 5. Ability to understand and the willingness to sign a written informed consent document for the Search Phase. 6. Patient willing to consider HCT 7. A preliminary search has identified: 1. An appropriate minimum 4/6 matched umbilical cord unit at intermediate resolution at HLA-A and B, and high resolution at HLA-DRB with a cell dose above 1 x 10(7) TNC/kg for a single umbilical cord blood (UCB) transplant AND 2. At least one potential 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1) unrelated donor with a probability of 70% AND 3. Availability of a potential related haploidentical donor. Exclusion Criteria for Search Phase: 1. Prior formal search was instituted 2. Diagnosis of acute promyelocytic leukemia (APL) 3. Known HLA matched related donor without contraindications to donate 4. Life expectancy severely limited by concomitant illness or uncontrolled infection Inclusion Criteria for Transplant Phase 1. High-risk AML for which transplant is recommend based on cytogenetic, molecular and morphologic features. Patients must meet institutional standards for disease control prior to transplant. 2. For MDS. IPSS-revised criteria of high or very high at diagnosis. 3. Subject meets institutional criteria for transplant and has acceptable organ and marrow function as defined below: 1. Serum bilirubin \< 2.0mg/dL unless Gilberts disease 2. Creatinine Clearance \> 45 mL/min.1.73m2 as estimated by modified MDRD equation 3. Left ventricular function 40% or greater 4. DLCO corrected for hemoglobin \>50% 5. KPS 70% or greater 4. An adequate graft for the defined donor type 1. Haplo-cord requires a haploidentical adult donor of 14 years of age and at least 50 kg, and a cord blood unit with at least 1.0 x 10(7) TNC/kg and a match of at least 4/6 by intermediate resolution for HLA-A and B and high resolution at DRB1. Donor provides standard of care consent for harvest following institutional policy. Any donor samples or donor research data would be obtained on separate donor research protocol. 2. For MUD requires a 7/8 or 8/8 HLA matched unrelated donor with high resolution matching at HLA-A, -B, -C, and DRB1. DP matching or DP permissive should be achieved when possible using T-cell epitope strategy. 5. Written informed consent for the transplant phase Exclusion Criteria for Transplant Phase 1. Life expectancy severely limited by concomitant illness or uncontrolled infection 2. HIV-positive