Inclusion Criteria:
* Malignant conditions or other life-threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
1. AML in 1st remission-- for patients whose AML does not have "good risk" cytogenetic features (i.e., t(8;21), (q22; q22.1); RUNX1-RUNX1T1, inv16).
2. Secondary AML in 1st remission
3. AML in 1st relapse or 2nd remission
4. CML not responding adequately to TKI therapy, CML in accelerated phase or blast crisis, or CML in CR after accelerated phase or blast crisis
5. Chronic myelomonocyte leukemia: CMML-1 and CMML-2.
6. Intermediate to high-risk primary or secondary myelofibrosis
* Patients aged ≥18 and ≤70 years old. Patients 65-70 years old will be examined as a separate cohort, since myeloablative regimens have been shown to be associated with increased morbidity, mortality, and toxicity in older patients, specifically, patients above 65 years of age (49).
* Patients may be of either gender or any ethnic background
* 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 any sex, gender, or 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 × ULN 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 (e.g., AML Chloroma obstructing the biliary tree). Patients with higher bilirubin levels due to causes other than active liver disease are also eligible with Pl approval e.g., patients with PNH, Gilbert's disease or other hemolytic disorders.
3. Renal: serum creatinine: within normal range 0.7-1.3 mg/dL or if serum creatinine is outside the normal range, then CrCl \> 45 mL/min (measured or calculated/estimated via Cockcroft-Gault formula).
4. Pulmonary: asymptomatic \[but sustained DLCO ≥ 50% of predicted (corrected for hemoglobin)\].
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 breast-feeding
* 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 viral hepatitis B core antibody (HBcAb) positivity, but absence of HBsAg, will be eligible if 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 specialist with the first detectable viral load.
* Presence of leukemia in the CNS
* 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 × 10\^6/kg after CD34+ selection
* Known sensitivity to components of CliniMACS® Prodigy CD34 System
* 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.
