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.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Infectious complications after CAR T-cell therapy: mechanisms, risk stratification, and prevention.
嵌合抗原受体(CAR)T 细胞疗法是复发或难治性 B 细胞恶性肿瘤的成熟治疗手段。
嵌合抗原受体(CAR)T细胞疗法已成为治疗复发或难治性B细胞恶性肿瘤的标准方法。尽管治疗成功,感染并发症仍是非复发性发病和死亡的重要原因。感染风险源于长期、多因素造成的免疫抑制状态,包括淋巴细胞清除化疗、治疗相关血细胞减少、持续CD4⁺ T细胞淋巴细胞减少、伴低丙种球蛋白血症的B细胞缺如,以及为控制免疫效应细胞相关毒性(如细胞因子释放综合征和免疫效应细胞相关神经毒性)而使用的皮质类固醇或细胞因子靶向治疗。感染谱随时间发生变化:输注后早期最常见细菌感染;后期病毒及机会性感染更突出,尤其见于免疫恢复延迟者。感染风险还受基础恶性肿瘤、既往治疗暴露及CAR-T产品类型影响。例如,靶向BCMA的CAR-T治疗感染负担较重,可能与浆细胞大量耗竭及体液免疫持续受损有关。预防感染需要结构化、个体化方案。常见措施包括抗病毒及肺孢子菌肺炎预防;在重度或持续性血细胞减少期选择性使用抗菌和抗真菌预防;对临床显著低丙种球蛋白血症患者进行免疫球蛋白替代;并根据免疫恢复情况制定疫苗接种计划。因此,协调一致且依据风险调整的预防措施,对于减少感染并改善CAR-T治疗后的长期结局至关重要。本综述总结现有证据及国际指南的主要建议,更新接受CAR-T治疗患者感染机制、风险分层和预防策略的概况。
Chimeric antigen receptor (CAR) T-cell therapy is an established treatment for relapsed or refractory B-cell malignancies. Despite therapeutic success, infectious complications remain a major contributor to non-relapsed morbidity and mortality. The risk of infection reflects a prolonged and multifactorial state of immunosuppression resulting from lymphodepleting chemotherapy, treatment-related cytopenia, sustained CD4 + T-cell lymphopenia, B-cell aplasia with hypogammaglobulinemia, and the use of corticosteroids or cytokine-directed therapies for the management of immune effector cell-associated toxicities (i.e., cytokine-release syndrome and immune effector cell-associated neurotoxicity). The spectrum of infections has evolved over time. Bacterial infections are observed most frequently in the early post-infusion period, whereas viral and opportunistic infections become more prominent later, particularly in patients with delayed immune recovery. Infection risk is also influenced by the underlying malignancy, prior exposure to treatment, and the type of CAR T-cell product used. For example, BCMA-directed CAR T-cell therapy has been associated with a higher infection burden, likely related to profound plasma cell depletion and sustained impairment of humoral immunity. Preventing infections in this setting requires a structured and individualized approach. Common strategies include antiviral and Pneumocystis jirovecii pneumonia prophylaxis, the selective use of antibacterial and antifungal prophylaxis during periods of severe or prolonged cytopenia, immunoglobulin replacement in patients with clinically significant hypogammaglobulinemia, and vaccination schedules guided by immune recovery. Therefore, coordinated and risk-adapted prevention is essential to minimize infectious complications and to improve long-term outcomes after CAR-T cell therapy. This review summarizes the current evidence and major recommendations of international guidelines to provide an updated overview of infection mechanisms, risk stratification, and preventive strategies for patients receiving CAR T-cell therapy.
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