PDF(Pubmed)
Abstract：
UNASSIGNED: The central nervous system (CNS) is the most common site of extramedullary invasion in acute lymphoblastic leukemia (ALL), and involvement of the CNS is often associated with relapse, refractory disease, and poor prognosis. Chimeric antigen receptor-T (CAR-T) cell therapy, a promising modality in cancer immunotherapy, has demonstrated significant advantages in the treatment of hematological malignancies. However, due to associated adverse reactions such as nervous system toxicity, the safety and efficacy of CAR-T cell therapy in treating CNSL remains controversial, with limited reports available.
UNASSIGNED: Here, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation.
UNASSIGNED: Our study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.
UNASSIGNED: Here, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation.
UNASSIGNED: Our study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.
摘要：
■中枢神经系统（CNS）是急性淋巴细胞白血病（ALL）中最常见的髓外侵袭部位，中枢神经系统的受累通常与复发有关，难治性疾病,预后不良。嵌合抗原受体T（CAR-T）细胞疗法，癌症免疫疗法的一种有希望的方式，在血液系统恶性肿瘤的治疗中显示出显著的优势。然而,由于相关的不良反应，如神经系统毒性，CAR-T细胞疗法治疗CNSL的安全性和有效性仍存在争议，提供有限的报告。
■这里，我们介绍了一例确诊为B-ALL的患者,尽管接受了多个周期的化疗和鞘内注射,但骨髓(BM)和脑脊液(CSF)均出现复发.自体CD19CAR-T细胞的输注导致BM和CSF完全缓解(CR)40天。然而,患者后来骨髓复发.随后，来自她哥哥的同种异体CD19CAR-T细胞被注入，导致CR在BM的又一成就。重要的是,在治疗期间,仅检测到1级细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)事件,对症处理显示改善.在随后的随访中，患者实现了5个月的无病生存期,并成功连接到造血干细胞移植.
■我们的研究为中枢神经系统受累不应被视为CAR-T细胞治疗的绝对禁忌症提供了支持。通过实施合适的管理和治疗策略，CAR-T疗法可以熟练地靶向CNS内的肿瘤细胞。这种治疗选择可能对复发或难治性患者特别有益。以及对传统疗法反应有限的中枢神经系统受累者。此外,CAR-T细胞疗法可以作为这些患者的同种异体造血干细胞移植(allo-HSCT)的有价值的桥梁。
■这里，我们介绍了一例确诊为B-ALL的患者,尽管接受了多个周期的化疗和鞘内注射,但骨髓(BM)和脑脊液(CSF)均出现复发.自体CD19CAR-T细胞的输注导致BM和CSF完全缓解(CR)40天。然而,患者后来骨髓复发.随后，来自她哥哥的同种异体CD19CAR-T细胞被注入，导致CR在BM的又一成就。重要的是,在治疗期间,仅检测到1级细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)事件,对症处理显示改善.在随后的随访中，患者实现了5个月的无病生存期,并成功连接到造血干细胞移植.
■我们的研究为中枢神经系统受累不应被视为CAR-T细胞治疗的绝对禁忌症提供了支持。通过实施合适的管理和治疗策略，CAR-T疗法可以熟练地靶向CNS内的肿瘤细胞。这种治疗选择可能对复发或难治性患者特别有益。以及对传统疗法反应有限的中枢神经系统受累者。此外,CAR-T细胞疗法可以作为这些患者的同种异体造血干细胞移植(allo-HSCT)的有价值的桥梁。
