Phase I/II MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Recipient Inclusion Criteria

1. 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 FLT3-ITD mutation

- 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

2. 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.

3. Cardiac ejection fraction ≥ 45%

4. Lung diffusion capacity ≥ 50%

5. Calculated creatinine clearance ≥ 50 cc/min

6. SGPT and SGOT ≤ 2.5 x ULN, 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

7. Availability of an 6/6 HLA matched sibling defined by Class I (HLA -A and B) serologic
typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.

8. Karnofsky performance status ≥70%

9. No prior myeloablative therapy or hematopoietic cell transplantation

Recipient Exclusion Criteria

1. Seropositive for any of the following: HIV ab, hepatitis B sAg , hepatitis C IgG Ab
positive, without definitive therapy for hepatitis C; or hepatitis C PCR positivity;
or hepatitis C IgM positivity

2. Uncontrolled bacterial, viral or fungal infection defined as currently taking
antimicrobial therapy and progression of clinical symptoms.

3. Uncontrolled CNS disease involvement

4. The recipient is pregnant or a lactating female.

5. Psychosocial circumstances that preclude the patient being able to go through
transplant or participate responsibly in follow up care

Donor Inclusion Criteria

1. Age ≥13 yo and ≤ 75 years

2. Karnofsky performance status of ≥ 70% defined by institutional standards

3. Seronegative for HIV 1 RNA 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 palladum antibody Syphillis 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 palladum 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

4. Must be 6/6 matched sibling donor as determined by HLA typing

5. Female donors of child-bearing potential must have a negative serum or urine beta-HCG
test within three weeks of mobilization

6. Capable of undergoing leukapheresis, have adequate venous access, and be willing to
undergo insertion of a central catheter should leukapheresis via peripheral vein be
inadequate

7. The donor or legal guardian greater than 18 years of age, capable of signing an
IRB-approved consent form.

Donor Exclusion Criteria

1. Evidence of active infection or viral hepatitis

2. HIV positive

3. Lactating female