Inclusion Criteria:
* Meets clinical criteria for leukapheresis or has a leukapheresis product previously collected and stored per recommended guidelines.
* 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.
* Willingness to participate in long term follow up study.
* Stated willingness to comply with all study procedures and be available for the duration of the study.
* 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.
* Aged 31 days to 30 years (inclusive) at time of consent and enrollment.
* Acute Lymphoblastic Leukemia (ALL) OR Non-Hodgkin Lymphoma (NHL) of B-cell origin that:
* 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.
* Performance score (Lansky or Karnofsky) of 50% or better;
* Unable to or declined to receive commercially available CD19 CAR-T Therapy.
Exclusion Criteria:
* Evidence of rapidly progressive disease without adequate salvage/bridging regimens as determined by the investigator.
* Active Graft-versus-Host Disease (GvHD).
* 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.
* 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)
* Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.
* Known HIV infection, or active Hepatitis B or active Hepatitis C infection.
