T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia

Inclusion Criteria:

- Patients with one of the high risk myeloid diseases as outlined below. Patients must
have ≤ 5% blasts on the last BM evaluation prior to starting the conditioning regimen.
Diseases included on this protocol include:

1. Acute Myeloid Leukemia (AML) in CR1 with intermediate or high risk features as
defined below:

°Cytogenetic abnormalities which are not considered "good risk" cytogenetic
features (i.e t(8:21), t(15:17), inv 16 without c-kit mutations.

And/or

- Therapy related AML with history of antineoplastic therapy (radiation and/or
chemotherapy) And/or

- Normal karyotype with mutations of FLT3, RUNX1, TP53 mutation, ASXL1 or any
others that are considered to be high risk

2. AML in ≥ 2nd remission

3. Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap
syndrome with:

°International prognostic scoring system risk score INT-2 or high risk at the
time of transplant evaluation.

And/or

- Any risk category if life-threatening cytopenia exists And/or

- Karyotype or genomic changes that indicate high risk for progression to
acute myelogenous leukemia, including abnormalities of chromosome 7 or 3,
mutations of TP53, or complex or monosomal karyotype.

4. Chronic myelomonocytic leukemia (CMML)

5. Chronic myeloid leukemia (CML) with the following features:

°Patients who have failed or are intolerant to BCR-ABL tyrosine kinase
inhibitors.

And/or

°CML with BCR-ABL mutation consistent with poor response to tyrosine kinase
inhibition (e.g T351l mutation)

6. Patients with severe aplastic anemia

- Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the EBMT
consensus criteria.

- Non-Hodgkin lymphoma meeting both of the following criteria:

- Responding to therapy prior to enrollment.

- Relapse after prior autologous bone marrow transplant or are ineligible for
autologous bone marrow transplant.

- Multiple Myeloma with disease in the following categories:

- Patients with relapsed multiple myeloma following autologous stem cell
transplantation who have achieved at least partial response following additional
chemotherapy

- Patients with high risk cytogenetics at diagnosis must have achieved at least a
partial response following autologous stem cell transplantation. Patients must
have complex karyotype, del17p, t4;14, and/or t14;16 by FISH and/or del13 by
karyotyping.

- Each patient must be willing to participate as a research participant and must sign an
informed consent form.

- Organ Function and Performance Status Criteria:

1. Patients be ≥ 18 years old.

2. Patients must have a Karnofsky (adult) or Performance Status ≥ 70%.

3. Patients must have adequate organ function measured by:

- Cardiac: asymptomatic or if symptomatic, then LVEF at rest must be ≥ 40% and
must improve with exercise.

- Hepatic: < 5x ULN ALT and < 2x ULN total serum bilirubin, unless there is
congenital benign hyperbilirubinemia.

- Renal: CrCl >50ml/min (measured or calculated/estimated).

- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted
(corrected for hemoglobin)

Exclusion Criteria:

- Prior allogenic hematopoietic stem cell transplantation

- Prior radiation therapy with 400cGY or more of TBI

- BM with increased fibrosis (Reticulin stain > 1/3)

- Active and uncontrolled infection at time of transplantation

- HIV infection

- Seropositivity for HTLV-1

- Inadequate performance status/ organ function

- Pregnancy or breast feeding

- Patient or guardian unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, follow-up, and research
tests.

Donor Inclusion and Exclusion Criteria:

- Must be a 10/10 HLA genotypically match related or unrelated donor at all A, B, C,
DRB1, and DQB1 loci, as tested by DNA analysis

- Able to provide informed consent for the donation process per institutional standards

- Meet standard criteria for donor collection as defined by the National Marrow Donor
Program Guidelines