人源化CD19 CAR-T细胞治疗儿童及青少年复发难治急性淋巴细胞白血病患者的疗效及安全性

OBJECTIVE: To investigate the efficacy and safety of humanized CD19-specific chimeric antigen receptor T cells（hCART19s）in treating children and young adults with relapsed/refractory acute lymphoblastic leukemia（R/R ALL）and to analyze relevant factors affecting its curative effect and prognosis. METHODS: We conducted a single-center clinical trial involving 31 children and young adult patients with R/R B-ALL who were treated with humanized CD19-specific CAR-T cells（hCART19s）from May 2016 to September 2021. RESULTS: Results showed that 27（87.1％）patients achieved complete remission（CR）or CR with incomplete count recovery（CRi）one month after CAR-T cell infusion. During treatment, 20（64.5％）patients developed grade 1–2 cytokine release syndrome（CRS）, and 4（12.9％）developed grade 3 CRS. Additionally, two patients had grade 1 neurological events. During the follow-up with a median time of 19.3 months, the median event-free survival（EFS）was 15.7 months（95％ CI 8.7–22.5）, and the median overall survival（OS）was 32.2 months（95％ CI 10.6–53.9）. EFS and OS rates were higher in patients who have undergone hemopoietic stem cell transplantation（HSCT）than in those without［EFS:（75.0 ± 12.5）％ vs（21.1 ± 9.4）％, P＝0.012; OS:（75.0 ± 12.5）％ vs（24.6 ± 10.2）％, P＝0.035］. The EFS and OS rates were significantly lower in patients with >3 treatment lines than in those with <3 treatment lines［EFS: 0 vs（49.5±10.4）％, P<0.001; OS: 0 vs（52.0±10.8）％, P<0.001］. To the cutoff date, 12 patients presented with CD19(+) relapse, and 1 had CD19(−) relapse. CONCLUSION: hCART19s are effective in treating pediatric and young adult R/R ALL patients, with a low incidence of severe adverse events and reversible symptoms. Following HSCT, the number of treatment lines can affect the long-term efficacy and prognosis of pediatric and young adult R/R ALL patients.