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.