![]() ![]() 2, 4, 5, 12 Here, we report the safety, efficacy, and correlative studies of CD19 CAR-T cells therapy in 10 pediatric patients in China. CAR-T cells targeting CD19 has successfully shown tremendous potential for B-cell lineage malignancies. 10, 11 Thus, developing efficient and molecular-targeted approaches to prolong the life-span of B-ALL children has become a vital priority in recent years. 1, 8, 9 Although adults with B-ALL display 10% higher relapse rates compare with pediatric patients and experience long-term event-free survival of less than 50%, it is reported that approximately 25% of pediatric patients have a relapse with CD19 negative or CD19 low and resulted in a considerable number of all childhood cancer deaths. 5- 7 In contrast, children's response rate was lower than that of adults, expanding from 68% to 90%. Recent studies indicated high initial remission rates of B-cell acute lymphoblastic leukemias (B-ALL) in adults with response rate ranging from 83% to 93%. Several groups have reported extended regressions of B-cell malignancies in patients receiving infusions of anti-CD19 CAR-T cells at different ages. 1 To date, more than 130 ongoing registered clinical trials are recruiting patients to investigate the safety and efficacy of variety design of CD19 CAR-T cells ( ). Since the first report of genetically engineered T cell with chimeric antigen receptor (CAR-T), CAR-T has become the hope for relapsed/refractory patients, especially for those with hematologic malignancy. Monthly assessments of CD19+ minimal residual disease (MRD) and CAR-T engraftment demonstrated the anti-CD19 activity of long-term engrafted CAR-T cell clones in one patient for more than 2 years. Four patients (40%) experienced serious (grade > 2) cytokine release syndrome (CRS) and three patients (30%) with obvious neurotoxicity. The pretreatment tumor burdens were high with a median bone marrow (BM) blasts percentage of 59.2% (7.31%-86.2%), excluding one patient only with brain infiltration of leukemia cells (0% BM blasts). All patients received a standard fludarabine and cyclophosphamide (FC) preconditioning regiment, followed by a CAR-T infusion with a median number of 0.5 (0.3-1.58) × 10 6 CAR+ T cells/kg. Here, we initiated a phase I study to treat 10 pediatric B-ALL patients using a CD19-targeted second generation CAR with a 4-1BB intracellular costimulatory domain. ![]() Persistent CAR-T cell engraftment is considered as the key to remain durable remission. ![]() However, around 50% of them relapse in 1 year. Ninety percent of relapse/refractory B-cell acute lymphatic leukemia (R/R B-ALL) patients can achieve complete remission (CR) after CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy. ![]()
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