决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
肿瘤细胞治疗研究
英文原题:Current management of central nervous system involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma.
Current management of central nervous system involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma.
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慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL/SLL)累及中枢神经系统(CNS)是一种不常见但日益被认识的临床实体。其表现高度异质,从轻微认知功能障碍到严重神经功能缺损不等,可发生于诊断时或复发时。诊断需要高度警惕,整合临床、影像学及脑脊液检查结果,同时排除循环CLL细胞的“旁观者”污染。治疗仍缺乏标准化方案,很大程度上外推自小型病例系列及其他血液系统恶性肿瘤的经验。使用具有可靠CNS穿透性的药物进行全身治疗是治疗的基石。Bruton酪氨酸激酶抑制剂及基于venetoclax的方案显示出良好的药代动力学和临床结局。
Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an uncommon but increasingly recognized clinical entity. It has a highly heterogeneous presentation, ranging from subtle cognitive dysfunction to severe neurological deficits, and may occur at diagnosis or relapse. The diagnosis requires a high index of suspicion, integrating clinical, radiologic, and cerebrospinal fluid findings while excluding "bystander" contamination by circulating CLL cells. Management remains non-standardized and largely extrapolated from small case series and experience with other hematologic malignancies.
Systemic therapy using medications with reliable CNS penetration is the cornerstone of treatment. Bruton tyrosine kinase inhibitors and venetoclax-based regimens demonstrate favorable pharmacokinetics and clinical outcomes. Intrathecal chemotherapy remains an important adjunct to systemic therapy, while radiotherapy is reserved for rapid symptom control or palliative purposes.
For relapsed or refractory CLL with CNS involvement, therapeutic decisions should consider prior treatment history and resistance mechanisms. Emerging modalities such as CAR-T cell therapy and allogeneic hematopoietic stem cell transplantation may offer durable remission in select patients. CNS involvement in CLL remains underdiagnosed and understudied.
Further research is needed to define optimal treatment strategies and improve survival outcomes in the era of targeted therapy.
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