Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors

Subject Inclusion Criteria:

- Patients with any of the following hematologic malignancies who are considered to be
eligible for allogeneic transplantation:

- Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk
for relapse including:

- Detectable minimal residual disease by either multicolor flow cytometry or
by genomic assay after initial induction therapy

- t(9;22) or detected BCR-ABL1 translocation by genomic methodologies

- BCR-ABL1-Like B-ALL [23] including mutations of IKZF1 or CRLF2

- Translocations or mutations involving 11q23 (MLL) gene.

- Hypodiploid karyotype

- Deletion of 9p

- Loss of 17p or TP53 mutation

- T-lymphocyte lineage antigen expression (T-ALL)

- Prior CNS or other extramedullary involvement

- WBC count ≥ 100,000 cells/μL at diagnosis

- Acute biphenotypic or bilineal leukemia in CR1

- Acute myeloid leukemia (AML) in CR1 with

- Detectable minimal residual disease (MRD) by either multicolor flow
cytometry or by genomic assay after initial induction therapy

- In the absence of MRD any intermediate or high risk features according to
the European LeukemiaNet 2017 guidelines indlucing:

- Mutated FL T3-ITD or FL T3-TKD

- Cytogenetic abnormalities not classified as favorable

- Cytogenetic abnormalities associated with myelodysplastic syndrome including
abnormalities of chromosome 5, 7, or 17p

- Complex karyotype or monosomal karyotype

- t(9;11)(p21.1;q23.3); MLL-KMT2A or other rearrangements of KMT2A

- t(9;11); BCR-ABL1

- Inversions or translocations of chromosome 3

- T(6;9)(p23;q34.1); DEK-NUP214

- Somatic mutation of RUNX1, ASX1 or TP53

- Extramedullary involvement

- WBC count ≥100,000 cells/μL at diagnosis

- Relapsed acute leukemia with ≤ 5% blasts in the bone marrow prior to
transplantation (i.e. CR2 or greater).

- Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap
syndrome with ≤ 10% blasts and at least one of the following:

- Revised International Prognostic Scoring System risk score of INT, HIGH, or VERY
HIGH at the time of transplant evaluation.

- Life-threatening cytopenias

- 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.

- Therapy related disease or disease evolving from other malignant processes.

- Chronic myelomonocytic leukemia (CMML) with ≤ 10% blasts prior to
transplantation.

- Chronic myeloid leukemia (CML) meeting one of the following criteria:

- Failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.

- CML with BCR-ABL mutation consistent with poor response to tyrosine kinase
inhibition (e.g. T351I mutation).

- CML with accelerated or blast phase with <10% blasts after therapy.

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

- Hodgkin lymphoma meeting both of the following criteria:

- Responding to therapy prior to enrollment

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

°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.

- Patients aged from birth through 65 years old are eligible.

- Patients must have Karnofsky/Lanksy performance status ≥70%.

- Cardiac left ventricular ejection fraction ≥50% at rest.

- Serum bilirubin ≤ 2 mg/dL. Patients with Gilbert's disease or ongoing hemolytic
anemia are acceptable if the direct bilirubin is ≤ 2 mg/dL.

- AST and ALT ≤ 2.5 x ULN unless thought to be disease related

- Estimated or measured creatinine clearance > 50 mL/min/1.73 m^2 body surface
area.

- Adult patients and pediatric patients capable of performing pulmonary function
studies must have hemoglobin adjusted pulmonary DLCO ≥50% of predicted.

Subject Exclusion Criteria:

- Persons with a HLA matched sibling donor or a 8/8 allele level HLA-matched unrelated
donor.

- Female patients who are pregnant or breast-feeding.

- Persons with an infection that is not responding to antimicrobial therapy.

- Persons who are seropositive for HIV.

- Persons with active/detectable central nervous system malignancy.

- Persons who do not meet the age and organ function criteria specified above.

- Presence of psychiatric or neurologic disease, or lack of social support that limits
the patient's ability to comply with the treatment protocol including supportive care,
followup, and research tests.

- Prior allogeneic hematopoietic cell transplantation are ineligible.

- Patients with history of other malignancy within 5 years of study therapy are
ineligible with the following exceptions: Low grade prostate cancer (Gleason's ≤6)
treated with curative intent, breast ductal carcinoma in situ treated with curative
intent, or nonmelanomatous skin carcinomas.

Donor Inclusion and Exclusion Criteria:

- Partially HLA-matched unrelated volunteers (allele level matched at 6-7 of 8 HLA loci:
-A, -B, -C, and -DRB1) are eligible.

- Related, haploidentical donors are eligible.

- Able to provide informed consent to the donation process

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