Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Recipient Inclusion Criteria

• Patients with the following diseases that are histopathologically confirmed are eligible
• Acute leukemia, primary refractory or beyond CR1, or minimal residual disease (MRD) positivity.
• High risk acute myeloid leukemia in CR1 with any of the following features:
• Complex karyotype(≥3 clonal chromosomal abnormalities)
• Any of the following high risk chromosomal abnormalities:
• Monosomal karyotype (-5, 5q-, -7, 7q-)
• t(11q23), t(9;11), inv(3), t(3;3) t(6;9) t(9;22)
• Normal karyotype with fms-like tyrosine kinase 3 (FLT3)-ITD mutation
• Other high risk features as determined by molecular studies, or clinical presentation as assessed by the treating physician
• Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
• Myelodysplastic syndromes
• Myeloproliferative syndromes
• Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
• Age ≥18 yo and ≤ 60 yo for patients in Cohort 1 only. At the start of Cohort 2A and beyond, eligibility will be expanded to allow pediatric patients age ≥ 13 yo.
• Cardiac ejection fraction ≥ 45%
• Lung diffusion capacity ≥ 50%
• Calculated creatinine clearance ≥ 50 cc/min
• Serum glutamic-pyruvic transaminase( SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3.0 x ULN (Upper limit of normal), unless elevated secondary to disease.
• Total bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome may be included at the discretion of the PI or where hemolysis has been excluded
• Availability of a HLA matched donor (related or unrelated) defined by Class I (HLA-A and B) serologic typing (or higher resolution) and Class II (HLA DRB1) molecular typing. An HLA matched donor is defined for this study to be a sibling that is HLA matched 6/6; or an unrelated donor that is HLA matched 6/6 or 5/6. A sibling may be a "half sibling."
• Karnofsky performance status ≥70%

Recipient Exclusion Criteria

• Seropositive for any of the following:

HIV ab; hepatitis B sAg; hepatitis C ab

• Prior myeloablative therapy or hematopoietic cell transplant
• Candidate for autologous transplant
• HIV positive
• Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms.
• Uncontrolled central nervous system (CNS) disease involvement
• Pregnant or a lactating female
• Positive serum or urine beta human chorionic gonadotropin (HCG) test in females of childbearing potential within 3 weeks of registration
• Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care

Donor Inclusion Criteria

• Age ≥13 yo and ≤ 75 years
• Karnofsky performance status of ≥ 70% defined by institutional standards
• Seronegative for HIV 1 RNA (polymerase chair reaction (PCR); HIV 1 and HIV 2 ab (antibody); HTLV 1 and HTLV 2 ab; PCR+ or sAg (surface antigen) hepatitis B ; or PCR+ or sAg for hepatitis C; negative for the Treponema pallidum antibody Syphilis screen; and negative for HIV 1 and hepatitis C by nucleic acid testing (NAT) within 30 days of apheresis collection. In the case that T pallidum antibody tests are positive, donors must:
• Be evaluated and show no evidence of syphilis infection of any stage by physical exam and history
• Have completed effective antibiotic therapy to treat syphilis
• Have a documented negative non treponemal test (such as RPR) or in the case of a positive non treponemal test must be evaluated by an infectious disease expert to evaluate for alternative causes of test positivity and confirm no evidence of active syphilitic disease
• Must be 6/6 matched sibling donor as determined by HLA typing
• Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
• Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukaph