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

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)

What this study is about