Depletion of CD45RA Positive Naive T Cells for the Prevention of Graft Versus Host Disease in Older Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia or Myelodysplastic Syndrome

Inclusion Criteria:

* PARTICIPANT: Age \> 60 years
* PARTICIPANT: Diagnosis of acute leukemia or myelodysplastic syndrome (MDS):

  * 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, Burkitt leukemia/lymphoma, mast cell leukemia, chronic myeloid leukemia \[CML\] with blast crisis or other chronic myeloproliferative neoplasm) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
  * Myelodysplastic syndrome (MDS) with a history of excess blasts (≥ approximately 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
* PARTICIPANT: Karnofsky performance status (KPS) ≥ 60% at pre-HCT evaluation
* PARTICIPANT: Ability to provide informed consent
* PARTICIPANT: Prior autologous or allogeneic HCT is permitted
* DONOR: Human leukocyte antigen (HLA) matching: HLA-identical related donors or unrelated donors matched for HLA-A, -B, -C, - DRB1, and -DQB1 by high-resolution deoxyribonucleic acid (DNA) typing. A single allele-level mismatch at HLA class I is permitted
* DONOR: Stem cell source: Donors must be able to undergo peripheral blood stem cell (PBSC) collection. Only G-CSF-mobilized PBSC are permitted as the hematopoietic stem cell (HSC) source on this protocol

Exclusion Criteria:

* PARTICIPANT: Circulating blasts:

  * Acute leukemia: circulating abnormal blasts detectable by standard pathology.
  * MDS: \> 5% circulating abnormal blasts by standard pathology
* PARTICIPANT: Patients with promyelocytic leukemia (APL)
* PARTICIPANT: Patients with active extramedullary disease are excluded. History of extramedullary disease is allowed if only minimal residual disease is present prior to HCT
* PARTICIPANT: Ejection fraction \< 35% (or shortening fraction \< 26% if ejection fraction \[EF\] unavailable)
* PARTICIPANT: Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
* PARTICIPANT: Patients with shortening fraction \< 26% may enroll if approved by a cardiologist
* PARTICIPANT: Carbon monoxide diffusing capability (DLCO) \< 40%, total lung capacity (TLC) \< 40%, forced expiratory volume in 1 second (FEV1) \< 40%, and/or requiring continuous supplemental oxygen
* PARTICIPANT: If pulmonary function tests (PFTs) cannot be obtained: any patient with room air oxygen saturation \< 89% during a 6-minute walk test (6MWT) will be excluded
* PARTICIPANT: Serum creatinine must be within institutional normal limits
* PARTICIPANT: If serum creatinine \> upper limit of normal, a 24-hour creatinine clearance will be performed; patients are excluded if \< 50 mL/min/1.73 m\^2
* PARTICIPANT: Exclude patients with any of the following:

  * Fulminant liver failure.
  * Cirrhosis with evidence of portal hypertension.
  * Alcoholic hepatitis.
  * Esophageal varices or history of variceal bleeding.
  * Hepatic encephalopathy.
  * Uncorrectable synthetic dysfunction (prolonged prothrombin time).
  * Ascites due to portal hypertension.
  * Bridging fibrosis.
  * Bacterial or fungal liver abscess.
  * Biliary obstruction.
  * Chronic viral hepatitis with total bilirubin \>3 mg/dL.
  * Symptomatic biliary disease
* PARTICIPANT: Active infectious disease requiring deferral of conditioning (per Infectious disease consult). Upper respiratory tract infection is not considered to represent an uncontrolled infection in this context
* PARTICIPANT: Fungal infection with radiologic progression despite appropriate antifungal therapy
* PARTICIPANT: Viral infection risk: HIV-1, HIV-2, human T-lymphotropic virus (HTLV) 1 or HTLV2 positivity or active infectious hepatitis
* PARTICIPANT: Patients with active central nervous system (CNS) leukemia at the time of treatment are excluded. A history of CNS leukemia is allowed if CNS disease has resolved prior to treatment initiation
* PARTICIPANT: Weight \> 110kg
* PARTICIPANT: Other malignancies:

  * Active non-hematologic malignancies (except non-melanoma skin cancers).
  * Non-hematologic malignancy in remission but with \> 20% risk of recurrence within 5 years.
  * Exclusion does not apply to indolent non-hematologic malignancies not requiring therapy
* PARTICIPANT: Patients with a life expectancy \< 12 months from co-existing disease other than the leukemia or MDS
* PARTICIPANT: Hypersensitivity to cyclophosphamide, fludarabine, tacrolimus or mycophenolate mofetil (MMF)
* PARTICIPANT: Inability to provide informed consent
* PARTICIPANT: Alternative treatment: Patients who are suitable for and willing to receive a standard high intensity (myeloablative) preparative regimen
* DONOR: Stem cell source restriction: Donors (or centers) that can exclusively provide bone marrow harvests
* DONOR: Medical contraindications: HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
* DONOR: Preexisting immunoreactivity:

  * Determined per institutional standard practices.
  * For patients with a 10/10 HLA allele-level match, panel reactive antibody (PRA) screens to class I and class II antigens are recommended before HCT. If PRA \>10%, then flow cytometric or B- and T-cell cytotoxic crossmatches must be obtained. The donor is excluded if any crossmatch is positive.
  * For patients with a Class I allele mismatch, flow cytometric or B- and T-cell cytotoxic crossmatches must be performed regardless of PRA results. A positive anti-donor cytotoxic crossmatch is an absolute exclusion.
  * Vector homozygosity: Donors are excluded if the patient is homozygous in the graft rejection vector against the donor's mismatched HLA class I allele
* DONOR: Donors donating outside of the United States of America (USA)