Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies

Eligibility Criteria

• * Aged 6 months to 80 years
• * Received prior or anticipated myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant
• * Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (\> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT:
• * Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Ambiguous lineage leukemia or lymphoma, Chronic Myelogenous leukemia (CML), CMML, MDS:
• * Evidence of active leukemia or lymphoma disease by flow cytometry, morphology, or cytogenetic evaluation within the marrow or extramedullary sites.
• * Hodgkin's Lymphoma that has failed or are intolerant of Brentuximab, Non-Hodgkin Lymphoma (NHL) including Grey Zone Lymphoma, Anaplastic large cell lymphoma (ALCL), and mantle cell lymphoma:
• * Evidence of lymphoma by morphology, Positron Emission Tomography (PET)/ Computed tomography (CT) uptake in a site of previous disease in the absence of other etiologies.
• * ARM C only includes patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease.
• * Karnofsky/Lansky score of ≥ 50
• * Agree to use contraceptive measures during study protocol participation (when age appropriate)
• * Patient or parent/guardian capable of providing informed consent.
• * T cell chimerism \> 94% if collected from recipient of allo-HSCT (performed within the last 6 months)
• * If the product is procured from the recipient in the autologous (Arm B) setting, the absolute lymphocyte count should be greater than or equal to 600 for procurement. Please note: If a patient has already undergone an allogeneic HSCT, it is NOT allowed to generate TAA-T from patient blood collected post-HSCT under Arm A or C
• * Patients with uncontrolled infections
• * Current evidence of GVHD \> grade 2 or bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis Pregnancy or lactating (female of childbearing potential) Recipient Inclusion criteria for initial TAA-T administration and for subsequent infusions
• * Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (\> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT:
• * Steroids less than 0.5 mg/kg/day prednisone or equivalent.
• * Karnofsky/Lansky score of ≥ 50.
• * Bilirubin \< 2.5 mg/dL, AST/ALT \<5x upper limit of normal, Serum creatinine \< 1.0 or 2x the upper limit of normal (whichever is higher).
• * Pulse oximetry of \> 90% on room air.
• * Absolute neutrophil count \> 250/ µL (may be supported with Granulocyte colony-stimulating factor (GCSF)).
• * Agree to use contraceptive measures during study protocol participation (when age appropriate).
• * Patient or parent/guardian capable of providing informed consent.
• * LVEF \> 50% or LVSF \> 27% (performed within the last 6 months) if history of TBI \>500 cGy for arm A and B.
• * Total chimerism \> 50%; or if cancer cells preclude this, donor T cell chimerism \> 50% (performed within the last 6 months).
• * Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal antibodies within 28 days prior to TAA-T infusion.
• * No investigational therapies (under IND, not extensively studied in the current clinical context) within 28 days prior to TAA-T infusion.
• * Uncontrolled infections
• * Active Bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis
• * Current evidence of GVHD \> grade 2 for Arm A and B; Active GVHD of any grade is exclusion for arm C patients.
• * Pregnancy or lactating (female of childbearing potential)