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.