HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide

Stratum 1 Recipient Inclusion Criteria:

   1. Age > 18 years and < 66 years (chemotherapy-based conditioning) or < 61 years (total
   body irradiation [TBI]-based conditioning) at the time of signing informed consent

   2. Planned MAC regimen as defined per protocol

   3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with
   age < 35 years

   4. Product planned for infusion is PBSC

   5. HCT Comorbidity Index (HCT-CI) < 5

   6. One of the following diagnoses:

      1. Acute myeloid leukemia (AML) acute lymphoblastic leukemia (ALL), or other acute
      leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating
      blasts or evidence of extra-medullary disease. Documentation of bone marrow
      assessment will be accepted within 45 days prior to the anticipated start of
      conditioning.

      2. Patients with myelodysplastic syndrome (MDS) with no circulating blasts and with
      < 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to
      lack of differences in outcomes with < 5% or 5-10% blasts in MDS). Documentation
      of bone marrow assessment will be accepted within 45 days prior to the
      anticipated start of conditioning.

   7. Cardiac function: Left ventricular ejection fraction > 45% based on most recent
   echocardiogram or multigated acquisition scan (MUGA) results

   8. Estimated creatinine clearance > 60 mL/min calculated by equation

   9. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO)
   corrected for hemoglobin > 50% and forced expiratory volume in first second (FEV1)
   predicted > 50% based on most recent pulmonary function test results

10. Liver function acceptable per local institutional guidelines

11. Karnofsky performance status (KPS) of > 70%

12. Subjects ≥ 18 years of age or legally authorized representative must have the ability
   to give informed consent according to applicable regulatory and local institutional
   requirements.

Stratum 2 Recipient Inclusion Criteria

   1. Age > 18 years at the time of signing informed consent

   2. Planned NMA/RIC regimen as defined per protocol

   3. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with
   age < 35 years

   4. Product planned for infusion is PBSC

   5. One of the following diagnoses:

      1. Patients with acute leukemia or chronic myeloid leukemia (CML) with no
      circulating blasts, no evidence of extramedullary disease, and with < 5% blasts
      in the bone marrow. Documentation of bone marrow assessment will be accepted
      within 45 days prior to the anticipated start of conditioning.

      2. Patients with MDS with no circulating blasts and with < 10% blasts in the bone
      marrow (higher blast percentage allowed in MDS due to lack of differences in
      outcomes with < 5% or 5-10% blasts in MDS.) Documentation of bone marrow
      assessment will be accepted within 45 days prior to the anticipated start of
      conditioning.

      3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including
      prolymphocytic leukemia) with chemosensitive disease at time of transplantation

      4. Patients with lymphoma with chemosensitive disease at the time of transplantation

   6. Cardiac function: Left ventricular ejection fraction > 45% based on most recent
   echocardiogram or MUGA results with no clinical evidence of heart failure

   7. Estimated creatinine clearance > 60 mL/min calculated by equation

   8. Pulmonary function: DLCO corrected for hemoglobin > 50% and FEV1 predicted > 50% based
   on most recent pulmonary function test results

   9. Liver function acceptable per local institutional guidelines

10. KPS of > 60%

11. Subjects ≥ 18 years of age or legally authorized representative must have the ability
   to give informed consent according to applicable regulatory and local institutional
   requirements.

Stratum 3 Recipient Inclusion Criteria

   1. Age > 1 years and < 21 years at the time of signing informed consent

   2. Partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age < 35
   years

   3. Product planned for infusion is BM

   4. Planned MAC regimen as defined per protocol

   5. One of the following diagnosis:

      1. AML in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts or
      evidence of extra-medullary disease. Pre-transplant MRD testing will be performed
      as per standard of practice at the treating institution. Patients with any MRD
      status are eligible and should be enrolled at the discretion of provider.
      Documentation of bone marrow assessment will be accepted within 45 days prior to
      the anticipated start of conditioning.

      2. Patients MDS with no circulating blasts and less than 10% blasts in the bone
      marrow. Documentation of bone marrow assessment will be accepted within 45 days
      prior to the anticipated start of conditioning.

      3. ALL in 1st remission or beyond with ≤ 5% marrow blasts, no circulating blasts, or
      evidence of extra-medullary disease. Pre-transplant MRD testing will be performed
      as standard practice at the treating institution with the goal of achieving MRD
      of <0.01%. Patients with any MRD status are eligible and should be enrolled at
      the discretion of provider. Documentation of bone marrow assessment will be
      accepted within 45 days prior to the anticipated start of conditioning.

      4. Other leukemia (mixed-phenotype acute leukemia [MPAL], CML, or other leukemia) in
      morphologic remission with ≤ 5% marrow blasts and no circulating blasts or
      evidence of extramedullary disease. Documentation of bone marrow assessment will
      be accepted within 45 days prior to the anticipated start of conditioning.

      5. Chemotherapy sensitive lymphoma in at least partial remission (PR)

   6. KPS or Lansky performance score ≥ 70%

   7. Cardiac function: Left ventricular ejection fraction of ≥ 50% and shortening fraction
   of ≥ 27% based on most recent echocardiogram

   8. Glomerular Filtration Rate (GFR) of ≥ 60ml/min/1.73m2 measured by nuclear medicine
   scan or calculated from a 24 hour urine collection

   9. Pulmonary function: DLCO corrected for hemoglobin, FEV1, and Forced Vital Capacity
   (FVC) of ≥50% if able to perform pulmonary function tests. If unable to perform
   pulmonary function tests, must have a resting pulse oximetry of >92% without
   supplemental oxygen.

10. Hepatic: Total bilirubin ≤ 2.5 mg/dL and alanine aminotransferase (ALT), aspartate
   aminotransferase (AST) < 3x the upper limit of normal

11. Legal guardian permission must be obtained for subjects < 18 years of age. Pediatric
   subjects will be included in age appropriate discussion in order to obtain assent.

12. Subjects ≥ 18 years of age or legally authorized representative must have the ability
   to give informed consent according to applicable regulatory and local institutional
   requirements.

Donor Inclusion Criteria:

   1. Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or
   7/8 (HLA-A, -B, -C, and -DRB1)

   2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DRB1, -DQB1,
   and -DPB1

   3. Age > 18 years and < 35 years at the time of signing informed consent

   4. Meet the donor registries' medical suitability requirements for PBSC or BM donation

   5. Must undergo eligibility screening according to current Food and Drug Administration
   (FDA) requirements. Donors who do not meet one or more of the donor screening
   requirements may donate under urgent medical need.

   6. Must agree to donate PBSC (or BM for stratum 3)

   7. Must have the ability to give standard (non-study) informed consent according to
   applicable donor regulatory requirements

Recipient Exclusion Criteria (Strata 1, 2 and 3):

   1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available

   2. Subject unwilling or unable to give informed consent, or unable to comply with the
   protocol including required follow-up and testing

   3. Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia,
   polycythemia vera, or MDS with grade 4 marrow fibrosis

   4. Subjects with a prior allogeneic HSC transplant

   5. Subjects with an autologous HSC transplant within the past 3 months

   6. Females who are breast-feeding or pregnant

   7. Uncontrolled bacterial, viral or fungal infection at the time of the transplant
   preparative regimen

   8. Concurrent enrollment on other interventional GVHD clinical trial (enrollment on
   supportive care trials may be allowed after discussion with Principal Investigators)

   9. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to
   transplant.

10. Patients who are HIV+ with persistently positive viral load. HIV-infected patients on
   effective anti-retroviral therapy with undetectable viral load within 6 months are
   eligible for this trial.

Donor Exclusion Criteria:

   1. Donor unwilling or unable to donate

   2. Recipient positive anti-donor HLA antibodies against a mismatched HLA in the selected
   donor determined by the presence of donor specific HLA antibodies (DSA) to any
   mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1,
   DRB3, DRB4, DRB5, -DQA1, -DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI)
   >3000 by microarray-based single antigen bead testing. In patients receiving red blood
   cell or platelet transfusions, DSA evaluation must be performed or repeated
   post-transfusion and prior to donor mobilization and initiation of recipient
   preparative regimen.