CD19.CAR-multiVSTs for Patients With CD19+ B-ALL or NHL Undergoing Related Allogeneic HSCT (CARMA)

Inclusion Criteria:

1. Diagnosis of CD19+ B-ALL or NHL undergoing related allogeneic HSCT, with no evidence of disease post-HSCT (Group A) OR minimal residual disease (MRD) at time of HSCT OR relapse post-HSCT (Group B).

   Morphologic relapse (for Group B) will be defined by accepted definitions in Section 5.6 of the full protocol, and measured by PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood.

   MRD will be defined as detection in blood or marrow of any of the following (at time of transplant or on post-transplant evaluation): a) Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient's leukemia cells pre-transplant on a post-transplant evaluation b) An immune globulin rearrangement known to be a disease marker for this patient c) A leukemia specific phenotype at a level of \> 0.01%95, 96 d) Mixed donor chimerism.
2. Age ≤ 75 years old
3. Patients with life expectancy ≥ 12 weeks
4. Patients with a Karnofsky/Lansky score ≥ 60
5. Related Donor approved for stem cell transplant
6. Patient or parent/guardian capable of providing informed consent
7. Patients with bilirubin less than or equal to 2x upper limit of normal
8. AST less than or equal to 3x upper limit of normal
9. Creatinine ≤2x upper limit of normal for age
10. Hemoglobin \>7.0 (can be a transfused value)
11. Pulse oximetry of \>90% on room air
12. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. The male partner should use a condom.
13. Available stem cell donor-derived CD19-CAR transduced multi-virus-specific cytotoxic T lymphocytes with 15% expression of CD19-CAR determined by flow-cytometry and \<10% cytotoxicity against patient or donor-derived (or other family member-derived) PHA blasts.

Exclusion Criteria:

1. Severe intercurrent infection: Patients with a concurrent bacterial infection must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
2. Evidence of graft versus host disease \>grade II
3. Pregnant or lactating
4. History of hypersensitivity reactions to murine protein-containing products.
5. Currently taking corticosteroids for therapy of GVHD at a dose of \>0.5mg/kg prednisone equivalent.
6. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3; History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
7. Patients who have received donor lymphocyte infusion (DLI) within 28 days.