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.