A Phase I Trial of Autologous CLL B Cells Transduced to Express Chimeric CD154 (ISF35)

Inclusion Criteria: 1. Subjects must have a diagnosis of B cell CLL, measurable disease, and an NCI-WG indication for treatment with one of the following: * Massive (\>6 cm below left costal margin) or progressive splenomegaly; * Massive (\>10 cm longest diameter) lymph nodes, nodal clusters, or progressive lymphadenopathy; * Progressive anemia; * Progressive thrombocytopenia; * Weight loss \> 10% body weight over the preceding 6 month period; * Fatigue attributable to CLL; * Fever or night sweats without evidence of infection; * Progressive lymphocytosis. 2. Subjects must be age 18 years or older. 3. Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. Both men and women participants must agree to use contraception for the duration of the study. 4. Subjects must have Zubrod performance status of ≤ 2 (Appendix B). 5. Subjects must have adequate hematologic, renal, hepatic, and coagulation function: * Adequate hematologic function: * Platelet count ≥ 50,000/μl; AND * Hemoglobin ≥ 10 g/dl (may be supported by erythropoietin or transfusion). * Adequate renal function: * Serum creatinine ≤ 1.5 times upper limit of normal; OR * Measured creatinine clearance ≥ 40 mL/min/1.73 m\^2. * Adequate hepatic function: * Total bilirubin ≤ 2.5 times upper limit of normal; AND * ALT ≤ 2.5 times upper limit of normal; AND * Adequate coagulation tests: * Prothrombin time international normalized ratio (INR) ≤ 2; AND * Partial thromboplastin time ≤ 1.66 times upper limit of normal 6. Subjects must be able to give written informed consent. Exclusion Criteria: 1. Presence of more than 55% prolymphocytes. 2. Chemotherapy (e.g., purine analogues, alkylating agents, or corticosteroids), antibody therapy, immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of enrollment into protocol or at any time during the study. 3. Ongoing toxicity from prior anti-neoplastic therapy. 4. Prior gene therapy or allogeneic stem cell transplantation. 5. Untreated autoimmune hemolytic anemia or immune thrombocytopenia. 6. Active infection requiring parenteral antibiotics. 7. Known HIV/HBV/HCV seropositivity. 8. Uncompensated hypothyroidism (defined as TSH greater than 4x upper limit of normal not treated with replacement hormone).