Targeted immunotherapy with CAR-modified T cells can produce potent antitumor responses. Complete remissions (CRs) and prolonged persistence have been documented in children and adults with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) treated with CD19-specific CAR-modified T cells (CTL019). This study evaluated outcomes after longer follow-up of 60 children and young adults with r/r ALL enrolled in the pediatric phase 1/2a trial of CTL019.1 The goals of the study were to determine: (1) safety and efficacy of CTL019 in pediatric patients with r/r CD19+ ALL, (2) safety and efficacy of CTL019 in pediatric patients with a history of central nervous system (CNS) involvement of ALL, and (3) relapse-free survival (RFS) and overall survival (OS) after CTL019. After informed consent, patient-derived T cells were transduced with a lentiviral vector encoding a CAR composed of anti-CD19 scFv, CD3z, and 4-1BB domains, activated and expanded ex vivo with anti-CD3/CD28 beads, and then infused at a dose of 107 to 108 cells/kg. Fifty-five of 60 patients received lympho-depleting chemotherapy during the week prior to cell infusion. Patients’ ages ranged from 20 months to 24 years. Of 60 patients, 73% had detectable disease prior to CTL019 cell infusion and 27% were minimal residual disease (MRD)-negative. Thirty-nine patients had been treated for relapse after prior stem-cell transplant (SCT). Seventeen patients had CNS disease within a year of infusion (n = 15) or at time of infusion (n = 2). One month after CTL019 infusion, 93% of patients were in CR. Forty-nine of these 56 patients (88%) achieved MRD <0.01% by flow cytometry. CTL019 cells were detectable in the cerebrospinal fluid for 98%. All patients achieved CR in the CNS, including patients with cerebrospinal fluid blasts detected the day prior to infusion. No CNS relapses have occurred. With median follow-up of 12 months (range, 1-43 months), 34 patients had ongoing CR, with 6 receiving subsequent therapy (5 SCT, 1 donor lymphocyte infusion). At 12 months, RFS was 60% and OS was 79% (95% confidence interval [CI], 70%-90%). At 24 months, OS was 61% (95% CI, 47%-69%). Twenty patients relapsed, 13 with CD19-negative disease. Cytokine release syndrome (CRS) occurred in 88% of patients. Severe CRS, which was seen in 27%, was associated with high disease burden and could be reversed with tocilizumab, an anti–IL-6R agent. Researchers conclude that single-agent CTL019 induces potent responses in patients with r/r ALL and can control CNS leukemia. Durable remissions were observed without subsequent SCT. Phase 2 registration trials of CTL019 are underway. 1. Maude S, et al. EHA 2016. Abstract S497.