中枢神经系统 B 细胞急性淋巴细胞白血病患者接受 IL-6 敲低的抗 CD19 CAR-T 治疗后的细胞因子释放综合征

To investigate the cytokine release syndrome (CRS) condition for central nervous system B-cell acute lymphocytic leukemia (CNS B-ALL) patients after CAR-Ts targeting CD19 with short hairpin RNA (shRNA)-IL-6 gene silencing technology (ssCART-19s) infusion.

This prospective observational research included a total of 12 cases of patients with CNS B-ALL from March 2017 to February 2020. ssCART-19 infusions (5 10 6 cells/kg) were given to patients for 3 consecutive days. After infusion, the temperature of all patients was detected constantly and the CRS was carefully monitored within 1 month after treatment. The serum levels of IL-2, IL-4, IL-6, IL-10, IFN- , TNF- , CRP and IL-17A were tested by enzyme-linked immunosorbent assay (ELISA) within 10 days after infusion.

All 12 CNS B-ALL patients showed CRS with 100% incidence rate, with 3 cases (25.00%) of CRS stage I and 9 cases (75.00%) with CRS stage II. No CRS stage III~V was observed. The overall response rate was 91.67% (11/12), with 10 patients (83.33%) showed CR and 1 case (8.33%) of PR. In 9 patients with CRS stage II, the temperature increased persistently, ranging from 4 days to 14 days after infusion, and decreased gradually after 14 days of nursing treatment. The hyperthermia condition started from 1 day after infusion and returned to baseline at the following 2-10 days of nursing treatment. The levels of the inflammatory factors increased markedly after ssCAR-T19s infusion for 2-3 days compared to the baseline, and gradually returned to the baseline after treatment. After 10 days of infusion, all inflammatory factors returned to normal levels.

ssCART-19s infusion induced short-term slight CRS with increased temperature and inflammatory factors, and no severe CRS was observed.