Inclusion Criteria:
1. Meets clinical criteria for leukapheresis or has a leukapheresis product previously collected and stored per recommended guidelines.
2. Provision of signed and dated consent form from parent or guardian (patients \<18), the patient themselves (\>18), or legally authorized representative (patient \>18 who lack decision-making capacity); Pediatric patients will be included in age-appropriate discussions and assent will be obtained for those \> 7 years of age, when appropriate, according to institutional standards.
3. Willingness to participate in long term follow up study.
4. Stated willingness to comply with all study procedures and be available for the duration of the study.
5. Males OR non-pregnant, non-breastfeeding females.
o Patients of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from the time of initial CAR T cell administration though 12 months following the final administration of investigational product.
6. Aged 31 days to 30 years (inclusive) at time of consent and enrollment.
7. Acute Lymphoblastic Leukemia (ALL) OR Non-Hodgkin Lymphoma (NHL) of B-cell origin that:
o Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC), or both.
Cohort One Criteria:
* Meets any one of the following conditions:
* Relapsed two or more times
* Relapsed at any time after allogeneic BMT
* Refractory to standard therapy as determined by the treating physician
* Meets criteria for BMT but is ineligible as determined by the treating physician
* Patient and/or parents declining BMT options and would prefer CAR-T Therapy.
* Non-Hodgkin Lymphoma includes all of the following:
* Diffuse large B-cell lymphoma (DLBCL)
* Burkitt Lymphoma
* Intermediate lymphoma between Burkitt and DLBCL
* Primary Mediastinal B-cell Lymphoma (PMBL)
* Follicular lymphoma
* High grade B cell lymphoma
* Transformed lymphoma
Cohort Two Criteria:
* B-ALL in first relapse with any one of the following conditions:
* High-risk genomic alterations at initial diagnosis such as KMT2A gene rearrangement, t(17;19), hypodiploidy, Ph-like mutations, BCR-ABL1 fusion (Ph+ ALL), iAMP21, and TP53 inactivating mutation/deletion.
* Isolated CNS relapse such that cranial radiation would be indicated as a component of standard salvage therapy.
* Down syndrome.
* Minimal residual disease (MRD) positivity of \> 0.01% by FACS or \> 0 clonal sequences by NGS in bone marrow post re-induction chemotherapy.
* Age 18 years or older. OR
* Newly diagnosed with persistent MRD ≥ 0.01% by flow cytometry in bone marrow at end of consolidation.
8. Performance score (Lansky or Karnofsky) of 50% or better;
9. Unable to or declined to receive commercially available CD19 CAR-T Therapy.
Exclusion Criteria:
1. Evidence of rapidly progressive disease without adequate salvage/bridging regimens as determined by the investigator.
2. Active Graft-versus-Host Disease (GvHD).
3. Active, uncontrolled, life-threatening infection that at the determination of the treating physician would preclude safe leukapheresis or tolerance of LD chemotherapy, cell infusion, or cytokine release syndrome.
4. Evidence of severe organ dysfunction as defined by:
* Myocardial dysfunction: Ejection fraction ≤ 40% or shortening fraction ≤ 28%, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings.
* Baseline oxygen saturation of ≤ 90% on room air
* Transaminases \> 10x upper limit of normal (ULN) or bilirubin \>2x the ULN, unless thought to be related to primary disease
* Estimated Cr clearance \<60 mL/min/1.73 m2 (if nuclear medicine GFR or other more specific testing exceeds this level than it can supersede the estimated clearance)
5. Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.
6. Known HIV infection, or active Hepatitis B or active Hepatitis C infection.
7. Prior gene therapy, including prior CAR-T cell.
