The authors describe the successful treatment of a patient with advanced, p53-deficient chronic lymphocytic leukemia (CLL) using autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting CD19. The CAR was designed to include CD137 (4-1BB) and CD3-zeta signaling domains, which enhanced in vivo expansion and persistence of the modified T cells. After infusion, the patient experienced a delayed onset of tumor lysis syndrome and complete remission, with no significant toxic effects other than lymphopenia. The engineered T cells persisted at high levels in the blood and bone marrow for at least 6 months, and a specific immune response was detected in the bone marrow, leading to the loss of normal B cells and leukemia cells expressing CD19. The remission lasted for 10 months. The study highlights the potential of CAR-T cell therapy in treating B-cell neoplasms and the importance of considering the inclusion of costimulatory domains to enhance the therapeutic effect.The authors describe the successful treatment of a patient with advanced, p53-deficient chronic lymphocytic leukemia (CLL) using autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting CD19. The CAR was designed to include CD137 (4-1BB) and CD3-zeta signaling domains, which enhanced in vivo expansion and persistence of the modified T cells. After infusion, the patient experienced a delayed onset of tumor lysis syndrome and complete remission, with no significant toxic effects other than lymphopenia. The engineered T cells persisted at high levels in the blood and bone marrow for at least 6 months, and a specific immune response was detected in the bone marrow, leading to the loss of normal B cells and leukemia cells expressing CD19. The remission lasted for 10 months. The study highlights the potential of CAR-T cell therapy in treating B-cell neoplasms and the importance of considering the inclusion of costimulatory domains to enhance the therapeutic effect.