背景:迄今为止,几乎所有关于嵌合抗原受体(CAR)-T细胞治疗B细胞急性淋巴细胞白血病(B-ALL)的研究均在难治性/复发性(r/r)或微小残留病阳性患者中进行.缓解期患者的CAR-T治疗尚未见报道。
目的:观察CAR-T细胞对预后不良的缓解期B-ALL患者的治疗效果。
结果:CAR-T治疗应用于2例处于缓解状态的B-ALL患者,这些患者预后因素较差,拒绝移植,1例因多种并发症无法接受标准化疗。这两名缓解期患者的CAR-T治疗程序与r/rB-ALL患者相同。编码由CD3ζ和4-1BB组成的第二代CAR的慢病毒载体用于产生CAR-T细胞。在细胞输注之前施用淋巴消耗剂氟达拉滨和环磷酰胺。每次T细胞输注后发生I级细胞因子释放综合征,没有神经毒性。CAR-T治疗后的非强化维持化疗和靶向药物使两名患者无需移植即可获得三年半以上的长期无事件生存期。
结论:CAR-T疗法可用于高危B-ALL患者,以避免移植,对于持久缓解,CAR-T联合维持治疗可能优于单独CAR-T.
BACKGROUND: To date, almost all studies regarding chimeric antigen receptor (CAR)-T cell therapy for B-cell acute lymphoblastic leukemia (B-ALL) were performed in refractory/relapsed (r/r) or minimal residual disease-positive patients. CAR-T therapy in remission patients has not been reported.
OBJECTIVE: To observe the treatment outcome of CAR-T cells for remission B-ALL patients with poor prognosis.
RESULTS: CAR-T treatment was applied to two B-ALL patients in remission status who had poor prognostic factors and refused transplantation, and one case was unable to accept standard chemotherapy owing to multiple complications. The procedure of CAR-T therapy in these two remission patients was the same as that in r/r B-ALL patients. Lentiviral vectors encoding second generation CARs composed of CD3ζ and 4-1BB were used to produce CAR-T cells. Lymphodepleting agents fludarabine and cyclophosphamide were administered prior to cell infusion. Grade I cytokine release syndrome occurred after each T-cell infusion and there was no neurotoxicity. CAR-T treatment followed by non-intensive maintenance chemotherapy and targeted drugs allowed both patients to obtain a long-term event-free survival of more than three and a half years without transplantation.
CONCLUSIONS: CAR-T therapy could be used in high-risk B-ALL patients as a consolidation to avoid transplantation, the combination of CAR-T and following maintenance therapy may be better than CAR-T alone for durable remission.