Uproleselan With Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for AML

Inclusion Criteria: * Age ≥12 months and ≤ 39 years * The minimum and maximum number of subjects enrolled on the study are 20 and 28, respectively. In order to ensure at least 70% of the population are under the age of 18 years of age, the number of subjects \>=18 years old will be limited as follows: * At least 7 of the first 10 subjects must be under 18 years old * At least 7 of the second 10 subjects must be under 18 years old * At least 6 of the last 8 subjects enrolled must be under 18 years old * Lansky/Karnofsky performance status ≥70% (see Appendix A) * Weight ≥10 kg * Acute myeloid leukemia that arises de novo or is secondary to: * cytotoxic chemoradiotherapy * myelodysplastic syndrome * a leukemia predisposition syndrome or inherited marrow failure syndrome other than ones associated with transplant-related morbidity and mortality. A predisposition resulting from a germline RUNX1 mutation is example of an eligible disorder. Fanconi Anemia and Dyskeratosis Congenita are examples of ineligible disorders. * Disease status: Multidimensional flow cytometry (MDF) to assess disease status for eligibility will be performed centrally by Hematologics. * In a first or second complete remission (defined as marrow with ≤1% leukemic blasts by MDF and no evidence of extramedullary disease) with minimal residual disease (MRD, defined as marrow with ≥0.05% leukemic blasts by MDF) after at least 2 cycles of induction/re-induction chemotherapy. * Have newly diagnosed disease or disease in first relapse that is refractory (defined as marrow with \>1% leukemic blasts by MDF or persistence of extramedullary disease) to at least 2 cycles of induction/re-induction chemotherapy. This sample will be used for eligibility as well as correlative biomarkers. Please see section 9.2 for details regarding collection, processing, and shipping of the sample. * Graft and Donor Types: * Patients must be receiving bone marrow or peripheral blood stem cells from a HLA identical related or HLA matched unrelated (allele level matched at A, B, C and DRB1 loci) donor. * Eligibility of prospective donors should be determined in compliance with requirements of 21 CFR Part 1271. This should include donor screening for COVID-19 exposure or infection. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-human-cell-tissue-or-cellular-or-tissue-based-product-hctp-establishments * Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document. Exclusion Criteria: * Participants who have had a previous hematopoietic stem cell transplantation * Participants who have had prior treatment with uproleselan * CNS 3 disease at time of admission for HSCT. Patients previously diagnosed CNS 3 disease that has improved (CNS1 or CNS2) will be eligible. (See Section 3.3 for definitions). * Down Syndrome * Fanconi Anemia, Dyskeratosis Congenita and other disorders associated with excess risk for transplant related toxicities * Acute Promyelocytic Leukemia * Multiply relapsed (≥2) disease * Pregnancy (positive serum beta-HCG) or breastfeeding Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with uproleselan, breastfeeding should be discontinued if the mother is treated with uproleselan. These potential risks also apply to other agents used in this study. * Absolute neutrophil count \<300/μL due to treatment (chemotherapy or immunotherapy). Patients with neutropenia due to disease related marrow dysfunction (refractory disease, underlying myelodysplasia or an underlying marrow failure disorder) will be eligible regardless of the absolute neutrophil count. However, enrolling centers must provide clear evidence that the neutrophil count is not rising, that the patient does not have an inadequately controlled infection (see section 3.2.15), and that the patient is on broad anti-fungal prophylaxis. Given the serious risk associated with starting conditioning in patients with severe neutropenia, centers are encouraged to delay transplant if they have any reason to believe that the absolute neutrophil count may improve. * Estimated GFR of \<60 mL/min/1.73 m2. Estimated GFR may be calculated using the CKD-EPI Creatinine Equation (2009) for patients ≥19 years or creatinine-based Bedside Schwartz equation (2009) for patients \<19 years. It is recommended that estimates be determined using the calculators found on the National Kidney Foundation website. the (https://www.kidney.org/professionals/KDOQI/gfr\_calculator). Any patient for whom these equations yields a GFR less than 90 mL/min/1.73 m2 should have radionucleotide testing. Measurement of 24-hour urine creatinine clearance is not an acceptable substitute for radionucleotide testing. * Cardiac ejection fraction \<50% or shortening fraction \<27% * Total bilirubin (with elevated direct bilirubin) or ALT \>2 X ULN. * Pulmonary disease with FVC, FEV1 or DLCO (corrected for hemoglobin) \<50 % predicted or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen * Active hepatitis B or C infection * Active, poorly controlled infections. In patients being treated for infection at the time of enrollment, source documentation of the results of all microbiologic, radiographic and pathology assessments performed for diagnosis and for evaluation of response to treatment will be required. * Patients with a known history of HIV are excluded, unless they meet all of the following conditions: * No history of HIV complications with the exception of CD4 count \<200 cells/mm3 * No antiretroviral therapy with overlapping toxicity such as myelosuppression * CD4 count \>500 cells/mm3 prior to the diagnosis of relapsed AML * HIV viral loads below the limit of detection * No history of highly active antiretroviral therapy (HAART)-resistant HIV * Patients who have received another investigational drug within 28 days or 5 half-lives (whichever is longer).