Treatments and/or Procedures

Study Criteria

Inclusion Criteria:

  -  Patients who are considered appropriate candidates for myeloablative, TBI-containing
     allogeneic hematopoietic stem cell transplantation and have one of the following
     diagnoses:

       -  Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission
          (< 5% marrow blasts by morphology).

       -  Acute myeloid leukemia (AML) in first or subsequent morphological remission (< 5%
          marrow blasts by morphology).

       -  Other acute leukemia or related neoplasm (including but not limited to 'mixed
          phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute
          leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma or
          chronic myeloid leukemia (CML) with blast crisis) in first or subsequent
          morphological remission (< 5% marrow blasts by morphology).

       -  Myelodysplastic syndrome (MDS) with a history of excess blasts (≥5% in marrow
          blasts by morphology) and a history of receiving cytoreductive therapy (including
          but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3
          months.

  -  Patient age 1-60 years old (inclusive) at the time of informed consent

       -  Patients aged 1-50 years old (inclusive) are eligible for TBI-based conditioning
          regimens

       -  Patients aged 1-60 years old (inclusive) are eligible for busulfan-based
          conditioning regimens (with or without TBI 4 Gy)

  -  Patient with an HLA-matched (HLA-A, B, C, DRB1, and DQB1 matched) related or unrelated
     donor capable of donating PBSC.

  -  Recipient informed consent/assent and/or legal guardian permission must be obtained.

  -  DONOR: HLA-matched related and unrelated donors (HLA-A, B, C, DRB1 and DQB1 matched
     based on high-resolution typing).

  -  DONOR: >= 18 years old.

  -  DONOR: Willing to donate PBSC.

  -  DONOR: Matched related donors:

       -  Must give informed consent using the related donor informed consent form.

       -  Must meet institutional donor eligibility criteria or be ineligible with
          statement that the donor is a first or second degree relative (exception 21 Code
          of Federal Regulations [CFR] 1271.65(b)(i)).

  -  DONOR: Matched unrelated donors:

       -  Must consent according to the applicable National Marrow Donor Program (NMDP)
          donor regulatory requirements.

       -  Must meet eligibility criteria as defined by the NMDP or be ineligible with
          statement of urgent medical need (exception 21 CFR 1271.65(b)(iii)).

       -  Must be vaccinated against COVID19. 'COVID vaccinated' is as defined by the NMDP
          and number of required doses may vary according to vaccine manufacturer and
          evolving guidelines.

Exclusion Criteria:

  -  Patients with central nervous system (CNS) involvement refractory to intrathecal
     chemotherapy and/or standard cranial-spinal radiation. A patient may have a history of
     CNS disease. However, any CNS disease must be cleared by the end of the
     pre-conditioning evaluation time frame. If CNS disease is identified on cerebrospinal
     fluid (CSF) evaluation within 30 days of the start of the preparative regimen a repeat
     CSF evaluation must be performed and show no evidence of disease in order for the
     patient to be eligible for the protocol.

  -  Patients on other experimental protocols for prevention of GVHD.

  -  Patient weight:

       -  Patients with HLA-matched related donors will be excluded if they weigh >= 100
          kg.

       -  Patients with HLA-matched unrelated donors will be excluded if they weigh >= 100
          kg and must be discussed with the Fred Hutch protocol principal investigator (PI)
          if they weigh >= 80 kg.

  -  Patients who are positive for human immunodeficiency virus (HIV)-1, HIV-2, human
     T-cell lymphotropic virus (HTLV)1 or HTLV2.

  -  Patients with uncontrolled infections for whom myeloablative HCT is considered
     contraindicated by the consulting infectious disease physician; i.e. patients with
     active infections require infectious disease consultation and documentation by the
     infectious disease team that myeloablative HCT is not considered to be
     contraindicated. Upper respiratory tract infection is not considered to represent an
     uncontrolled infection in this context.

  -  Patients with organ dysfunction, including:

       -  Renal insufficiency (creatinine > 1.5 mg/dl) at the time of evaluation for the
          protocol. Patients with a known history of creatinine > 1.5 mg/dl or a current
          serum creatinine above the normal range for age must have a current creatinine
          clearance of > 60 ml/min/1.73 m^2 (measured by 24-hr urine specimen or nuclear
          glomerular filtration rate [GFR]).

       -  Left ventricular ejection fraction < 45%.

       -  Carbon monoxide diffusing capability (DLCO) corrected < 60%. Patients who are
          unable to perform pulmonary function tests (for example, due to young age and/or
          developmental status) will be excluded if the oxygen (O2) saturation is < 92% on
          room air.

       -  Liver function abnormality. Patients who have liver function test (LFT)s
          (specifically, total bilirubin, aspartate aminotransferase [AST] or alanine
          aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by
          a gastrointestinal (GI) physician unless there is a clear precipitating factor
          (such as an azole, MTX, trimethoprim-sulfamethoxazole, or another drug). If the
          GI physician considers that HCT on the protocol is contraindicated, that patient
          will be excluded from the protocol. Patients with Gilbert's syndrome and no other
          known liver function abnormality or with reversible drug-related transaminitis do
          not necessarily require GI consultation and may be included on the protocol.

  -  Patients who have received previous myeloablative allogeneic or autologous
     transplantation.

  -  Patients with a life expectancy < 12 months from co-existing disease other than the
     leukemia or MDS.

  -  Patients who are pregnant or breast-feeding.

  -  Patients of childbearing age who are presumed to be fertile and are unwilling to use
     an effective birth control method or refrain from sexual intercourse during and for 12
     months post-HCT.

  -  Patients with any other significant medical conditions that would make them unsuitable
     for transplantation, as determined by the PI.

  -  Patients with a known hypersensitivity to tacrolimus or MTX

  -  Patients who have received checkpoint inhibitors within three months of
     transplantation unless an exception is made by the PI

  -  DONOR: Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active
     hepatitis B or hepatitis C virus infection. Test must be performed using Food and Drug
     Administration (FDA) licensed, cleared, and approved test kits (serological and/or
     nucleic acid amplification test [NAT] and/or other approved testing) in a Clinical
     Laboratory Improvement Act (CLIA)-certified laboratory.

  -  Unrelated donors donating outside of the USA.