Inclusion Criteria:
1. Documented informed consent of the participant and/or legally authorized representative.
2. Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study PI approval.
3. Age ≥ 18 years.
4. ECOG ≤ 2.
5. Life expectancy ≥ 16 weeks.
6. Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma
7. Relapsed/refractory disease after failure of ≥ 2 prior lines of therapy.
8. Evidence of active BAFF-R expression at the time of enrollment.
9. Recovered to ≤ Grade 1 from the acute toxic effects (except alopecia) of prior anti-cancer therapy.
10. No known contraindications to leukapheresis, steroids or tocilizumab.
11. Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or CD19-CAR T cells).
For participants who had prior CD19-CAR T cell therapy:
\- At least 90-days has elapsed since participant received last CD19-CAR T cell therapy.
AND
\- Persistence of prior CD19-CAR T cells must be evaluated and found to be \<5% prior to leukapheresis procedure
12. Participants with CNS involvement by leukemia (CNS2 and asymptomatic CNS3) may be considered eligible after discussions with the study team.
13. Total serum bilirubin ≤ULN (unless has Gilbert's disease, then ≤3.0)
14. AST ≤ ULN
15. ALT ≤ ULN
16. Creatinine clearance of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula
17. Left ventricular ejection fraction (LVEF) ≥ 50%
18. O2 saturation ≥ 92% on room air.
19. Seronegative for HIV Ag/Ab combo, HCV\*, and active HBV (Surface Antigen Negative)
\*If positive, Hepatitis C RNA quantitation must be performed and must be undetectable.
20. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
21. QuantiFERON-TB Gold or equivalent\*
\*Results do not impact patient eligibility, however the test must be initiated prior to enrollment
22. Agreement by females and males of childbearing potential\^ to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.
\^Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).
23. A complete liver evaluation (which includes ultrasound elastography, MRI of the liver and a hepatology consult) may be done if needed based on PI's recommendation.
24. Evaluation of acquired hemochromatosis (indicated through MRI of the liver and elevated levels of Ferritin) is recommended for participants who have undergone multiple transfusions and prior alloHCT.
Exclusion Criteria:
1. Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment.
2. Immunosuppressant medications within 1 months prior to protocol enrollment.
3. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
4. Auto-immune disease or active GVHD within 4 months prior to protocol enrollment requiring systemic immunosuppressant therapy.
5. Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification.
6. Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within 2 weeks of enrollment.
7. Any abnormal liver enzyme levels (as defined ≥ULN in ALT, AST, Bilirubin and Alkaline Phosphatase levels) at time of enrollment
8. . Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
10. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
11. History of venous occlusive disease (VOD), or GvHD.
a. Subjects with a history of the following GvHD may still be included in the study: i. Resolved Grade 2 or less steroid-sensitive acute skin GvHD ii. Grade 1 gastro-intestinal (GI)-GvHD developed within 100 days post prior alloHCT.
iii. Limited chronic GvHD
12. History of stroke or intracranial hemorrhage within 6 months of enrollment.
13. History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 3 years.
14. Clinically significant uncontrolled illness.
15. Active systemic uncontrolled infection requiring antibiotics.
16. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
17. Females only: Pregnant or breastfeeding.
18. Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
19. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
