• Evaluate safety of escalating doses of autologous peripheral blood CTLs and EBV-specific cytotoxic CTLs, both genetically modified to express artificial T-cell receptors targeting the CD19 molecule. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  

• To measure the differential survival and function of CD19CAR transduced PBTLs and EBV-CTLs in vivo, in particular to determine if CD19CAR transduced EBV-CTLs survive longer than CD19CAR-CD28 transduced PBTLs. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  
• To measure the anti-tumor effects of CD19CAR transduced T- lymphocytes in patients with low and intermediate-grade NHL or B-CLL. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  

Dosing: Three dose levels will be evaluated. Using the modified continual reassessment method, cohorts of size two will be enrolled at each dose level. Each patient will receive one injection of each according to the dosing schedules listed below.

For patients with relapsed/refractory intermediate grade lymphoma treated with high dose chemotherapy followed by autologous stem cell transplantation, treatment day 0 will be at least 14 days after the date of autologous stem cell transplant, unless there is clear evidence of relapse. In this case, T-cell infusion can occur at any time after autologous stem cell transplant.

For patients in all other eligible settings, if the absolute T lymphocyte (CD3+) count before treatment is greater than 500, the patients will receive one dose of cyclophosphamide (1.5 g/m2) to induce mild lymphopenia.

GROUP 1 PBTL CD19CAR-28 zeta EBV-CTL CD19CAR zeta Day 0 2x10exp7 cells/m2 2x10exp7 cells/m2

GROUP 2 PBTL CD19CAR-28 zeta EBV-CTL CD19CAR zeta Day 0 1x10exp8 cells/m2 1x10exp8 cells/m2

GROUP 3 PBTL CD19CAR-28 zeta EBV-CTL CD19CAR zeta Day 0 2x10exp8 cells/m2 2x10exp8 cells/m2

Premedication: Patients will be pre-medicated with diphenhydramine 0.5 to 1mg/kg IV (max 50 mg) and acetaminophen 10mg/kg p.o. (max 650 mg). Steroids should be avoided given their detrimental effect on the survival of the infused T cells.

Anti-emetics: Anti-emetics in appropriate dosage for each patient will be prescribed as necessary.

Administration: The first of the two T-cell products transduced with CD19CARzeta or CD19CAR-28zeta will be given by intravenous injection over 1 to 10 minutes, and the IV flushed with saline. Then the second product will be given by intravenous injection over 1 to 10 minutes and the IV flushed with saline.

- Between 2 and 30 mls of cells will be infused. - The volume of infusion will depend upon the concentration of the cells when frozen, the dose level, and the size of the patient.

Post-administration Patient Treatment: - Outpatients may be treated in the clinic. - Monitoring will be undertaken according to institutional standards - Patients will receive supportive care for acute or chronic toxicity, including blood components or antibiotics, and other interventions as appropriate. - All treatment will be given at CAGT in The Methodist Hospital or at GCRC at Texas Childrens Hospital - Patients should preferably not receive other anti-neoplastic agents for six weeks after infusion of transduced T-cells (for purposes of evaluation). However patients may receive other therapy if needed at the discretion of their attending physician.