Inclusion Criteria:

• Patients aged ≥ 18 years old.
• Patients with any of the following hematologic malignancies for which allo-HCT is indicated, including:
  • Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1.
  • Relapsed AML in ≥ CR2.
  • Acute leukemias of ambiguous lineage in ≥ CR1.
  • Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR2.
  • CML meeting one of the following criteria:
  • Failed response to or intolerant to BCR-ABL tyrosine kinase inhibitors (TKIs).
  • CML with BCR-ABL mutation consistent with poor response to TKIs (e.g., T315I mutation)
  • CML in accelerated phase or blast crisis with <10% blasts after therapy, or in second chronic phase.
  • Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN overlap syndromes with least one of the following:
  • Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
  • Life-threatening cytopenias.
  • Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
  • Therapy related disease or disease evolving from other malignant processes.
  • Chronic myelomonocytic leukemia (CMML-1 or CMML-2).
  • Severe aplastic anemia.
  • Relapsed Hodgkin lymphoma meeting both of the following criteria:
  • Responding to therapy prior to enrollment.
  • Relapse after autologous HCT or are ineligible for autologous HCT.
  • Relapsed non-Hodgkin lymphoma meeting both of the following criteria:
  • Responding to therapy prior to enrollment.
  • Relapse after prior autologous HCT or are ineligible for autologous HCT.
  • High-risk multiple myeloma following autologous HCT or relapsed multiple myeloma following autologous HCT with chemosensitive disease.
• Adequate organ function is required, defined as follows:
  • • Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.
    • AST, ALT, and alkaline phosphatase < 3 times the upper limit of normal unless thought to be disease-related.
    • Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft Gault)
    • LVEF ≥ 45% by MUGA or resting echocardiogram.
    • Pulmonary function (FEV1 and corrected DLCO) ≥ 50% predicted.
• Adequate performance status of ECOG ≤ 2.
• Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

• Patients with active extramedullary disease.
• Patients with active central nervous system malignancy.
• Active and/or uncontrolled infection at the time of allo-HCT.
• Patients who have undergone previous allo-HCT.
• Patients who have undergone previous autologous HCT within the last 6 months, with the exclusion of high-risk multiple myeloma patients.
• Patient seropositivity for HIV I/II and/or HTLV I/II.
• Females who are pregnant or breastfeeding.
• Patients unwilling to use contraception during the study period.
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol.

Donor Inclusion and Exclusion Criteria:

• Must be a 10/10 HLA genotypically matched related or unrelated donor at A, B, C, DRB1, and DQB1 loci, as tested by DNA analysis.
• Able to provide informed consent for the donation process per institutional standards.
• Meet standard criteria for donor collection as defined by t