Inclusion Criteria:

• MDS patients who qualify for transplant, for which CD34+ selected, T-cell-depleted allogeneic hematopoietic stem cell transplantation is indicated

  1. Patients with high-risk features with a score equal to or higher than 4.5 using the IPSS-R.
  2. Patients with therapy-related MDS and patients with transfusion-dependent MDS are high-risk patient cohorts that are eligible independent of Revised International Prognostic Scoring System (IPSS-R) scoring.
• Patient's age is from ≥18 to ≤72 years old.
• Patients must have an appropriately matched donor (MRD 8/8, MUD 8/8, or MMUD 7/8 [mismatch at HLA-A, B or DR-B1 locus])
• Patients may be of either gender or any ethnic background.
• Patients must have a Karnofsky (adult) Performance Status of at least 70%

• Patients must have adequate organ function measured by:

  1. Cardiac: asymptomatic; left ventricular ejection fraction (LVEF) at rest must be ≥ 50%.
  2. Hepatic: < 3 × upper limit of normal (ULN) aspartate aminotransferase (AST) and < 1.5 × ULN total serum bilirubin unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible for Pl approval e.g., patients with paroxysmal nocturnal hemoglobinuria (PNH), Gilbert's disease, or other hemolytic disorders.
  3. Renal: serum creatinine: within the normal range 0.7-1.3 mg/dL or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 45 mL/min (measured or calculated/estimated via Cockcroft-Gault formula).
  4. Pulmonary: asymptomatic [but sustained diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% of predicted (corrected for hemoglobin)].
• Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

• Individuals who are pregnant or breastfeeding

• Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.

  1. Patients cured of Hepatitis C for ≥3 years prior to enrollment are permitted
  2. Patients with detectable hepatitis B surface antigen (HBsAg) will be excluded. Patients with detectable hepatitis B surface antigen (HBsAg) are excluded. Patients with viral hepatitis B core antibody (HBcAb) positivity, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable and if they are willing to be on hepatitis B antiviral prophylaxis and undergo monitoring for HBV reactivation (every 12 weeks while on immune suppression) per institutional protocols. Patients will be referred promptly to hepatology specialists with the first detectable viral load.
• Symptomatic cardiac disease (angina, congestive heart failure) and/or LVEF <50%
• History of cardiovascular disease, including but not limited to myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 6 months prior to the initiation of study or congestive heart failure (New York Heart Association [NYHA] class III-IV)
• Patients who subsequently receive a non-T-cell-depleted transplant
• Stem cell count <3.0 × 106/kg following CD34+ selection
• Known sensitivity to components of CliniMACS® Prodigy CD34 System 8. Have a history of other active malignancy(ies) unless the patient has been disease-free for at least 2 years and is deemed by the treating Investigator to be at low risk for recurrence of that malignancy; or the only prior cancer is curatively treated cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin.