Background: Complete remission (CR) rates for B-ALL in adults is high (>80%), but overall survival remains low (approximately 30%). Patients with relapsed disease have a very poor prognosis with a median survival measured in months. Therefore, there is a dire need for novel therapies for adults with relapsed or minimal residual B-ALL. To this end we have developed a novel T cell therapy for B cell malignancies using patient derived T cells genetically modified to express the 19-28z chimeric antigen receptor (CAR), an artificial T cell receptor specific to the CD19 antigen expressed on most B cell tumors. Human T cells retrovirally modified to express the 19-28z CAR successfully targets and eradicates B cell tumors in vitro and systemic human B cell cancers in mice. We have recently published the results of our initial Phase I clinical trial experience (Brentjens, Rivière et al., Blood 2011) utilizing this technology in adults with chronic lymphocytic leukemia. These results suggest clinical activity and demonstrate a persistence of 19-28z+ T cells that is inversely associated with tumor burden. These studies suggest that 19-28z+ T cells may be particularly effective in relapsed B-ALL because these tumors retain a degree of chemotherapy sensitivity, which will allow the infusion of T cells after salvage chemotherapy when patients have low tumor burdens. To our knowledge, this is the first clinical trial using autologous CD19 targeted T cells in adults with B-ALL. Methods: We are enrolling patients to a Phase I T cell dose escalation trial (NCT01044069). Adults with CD19+ B-ALL classified as a CR, relapsed, or refractory are eligible for enrollment. After patients are enrolled they are leukapheresed to obtain peripheral blood T cells, which are then retrovirally transduced to express the 19-28z CAR and expanded in our GMP gene transfer facility. Enrolled patients with relapsed or refractory B-ALL undergo a cycle of re-induction chemotherapy and conditioning cyclophosphamide followed by infusion of autologous 19-28z+ T cells. To date, 11 patients have been enrolled and 2 patients have been infused with 19-28z+ T cells.