Inclusion Criteria:

• AML or MDS patients eligible to receive first allogeneic HCT. Eligibility inclusion for HCT is defined as per University of Michigan bone marrow transplant (BMT) standard of care criteria

• Presence of high-risk AML/MDS with probable biallelic TP53 deletion or mutation status, defined by one of the following in prior blood or bone marrow assessments:

  • TP53 loss by karyotype (chromosome 17 or 17p deletion) or single nucleotide polymorphism (SNP) (Cancer Microarray) AND ≥ one clonal TP53 mutation by next generation sequencing (NGS) (VAF > 10%).
  • ≥ one TP53 mutation by NGS testing (with VAF > 40%)
  • ≥ two distinct TP53 mutation(s) by NGS (VAF >10%)

• Evidence that at least one TP53 allele harbors a structural TP53 missense mutation. In cases where the mutation type is unclassified, molecular pathology assessment is required to determine if one of the lesions is a missense mutation (as described in NGS report)

• Patients may be enrolled with either active disease or in morphological remission, provided the bone marrow blast count on the pre-HCT assessment does not exceed 30%

• Age > 21 years at enrollment and receiving allogeneic HCT in the adult transplant program

• Karnofsky performance score (KPS) ≥ 70%

• Documentation of adequate pulmonary function by forced expiratory volume and 1 second (FEV1) ≥ 50% of predicted, forced vital capacity (FVC) ≥ 50% of predicted and DLCO (corrected for hemoglobin) ≥ 50% of predicted (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Transthoracic echocardiogram with ejection fraction ≥ 50% (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Estimated glomerular filtration rate ≥ 50% ml/min/1.73m^2 by the Cockcroft-Gault equation. Glomerular filtration rate (GFR) should be corrected for body surface area (BSA) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Total bilirubin ≤ 2 x upper limit of normal (unless directly attributed to Gilbert's Syndrome) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Electrocardiogram (ECG) with corrected QT (QTc) ≤ 450 msec (using the Framingham correction) (must meet all criteria at time of enrollment based on standard of care pre HCT testing)

• Availability of an 8 of 8 HLA matched unrelated donor with matching at HLA A, B, C and DRB1

• Availability of a peripheral blood stem cell (PBSC) product

• Ability to understand and the willingness to sign a written informed consent

• Willingness to agree to use adequate contraception methods (subjects of reproductive potential only):

  • Females of reproductive potential must agree to use effective contraception (e.g., hormonal contraception, intrauterine device, tubal occlusion, vasectomized partner, abstinence) during treatment with ATO and for 6 months after the final dose.
  • Males with female partners of reproductive potential must agree to use effective contraception during treatment with ATO and for 3 months after the final dose

Exclusion Criteria:

• Uncontrolled infections. Patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic, clinical and/or culture) that the infection is well controlled
• Patients may NOT have evidence or symptoms of central nervous system (CNS) disease at the time of enrollment
• HIV or human t-lymphotropic virus (HTLV) 1 / HTLV 2 (seropositivity and/or polymerase chain reaction [PCR] positivity)
• Pregnant and nursing mothers are excluded
• Any physical, psychological or psychosocial condition that, in the opinion of the investigator, would pose unacceptable risk to the patient
• Other malignancy requiring systemic therapy or with life expectancy of < 1 year
• Receipt of prior allogeneic HCT
• History of severe cardiac conduction abnormalities (complete heart block, Left Bundle Branch Block, Torsades de Pointes, or other ventricular arrythmias). History of any cardiac arrhythmia (e.g. rate controlled atrial fibrillation) is not an exclusion
• QTc > 450 msec (using the Framingham correction)
• Patients under 40 years of age at time of evaluation will be screened for Shwachman-Diamond syndrome (SDS), which is a rare, inherited disorder characterized primarily by exocrine pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. These patients commonly progress to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Given potential for increased liver toxicities in this population, these patients will be excluded from the study. All patients under 40 years old will be screened through the University of Michigan Prevention Genetics Clinic prior to enrollment
• Patients with known hypersensitivity to arsenic