CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.
Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.
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我们发现 CAR-T 接受者的认知保持稳定,并发现治疗反应与感知认知随时间变化之间存在关联。
CAR-T 细胞疗法(CAR-T)为癌症患者带来持久缓解,但人们担心细胞因子释放综合征(CRS)和神经毒性可能影响幸存者的认知功能。我们评估了CAR-T 接受者的长期认知功能,并考察了与认知随时间变化相关的因素。
我们在成人患者接受 CAR-T 前及 6 个月随访时评估了感知认知(Functional Assessment of Cancer Therapy-Cognition)和神经认知表现(标准化神经心理学测试组合)。我们使用配对 T 检验检查了认知结局的变化。我们使用单变量和多变量线性回归模型,探讨患者、疾病或 CAR-T 特异性因素是否与认知随时间的变化相关。
我们纳入了106名参与者(平均年龄=62.7岁,60.4%为男性,56.6%诊断为non-Hodgkin s lymphoma),其中70名报告了感知认知数据,26名在两个时间点均接受了神经认知表现评估。从基线到CAR-T 后6个月,感知认知(P = .560)、总体神经认知表现(P = .924)或神经认知领域(P s > .05)均无变化。在6个月时,相对于基线,32.9%报告感知认知改善,47.1%稳定,20.0%下降。在未调整分析中,疾病进展(= -8.86,P = .012)、基线升高的C-reactive protein(= -5.60,P = .076)和基线神经系统合并症(= -11.4,P = .052)在数值上与随时间更差的感知认知相关。在多变量分析中,只有疾病进展与随时间更差的感知认知具有统计学显著相关性(= -7.32,P = .032)。
CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.
We assessed perceived cognition (Functional Assessment of Cancer Therapy-Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up. We examined changes in cognitive outcomes using paired T-tests. We used univariate and multivariate linear regression models to explore whether patient-, disease-, or CAR-T specific factors were associated with change in cognition over time.
We included 106 participants (mean age = 62.7 years, 60.4% male, 56.6% diagnosed with non-Hodgkin s lymphoma), of whom 70 reported perceived cognition data and 26 underwent neurocognitive performance assessments at both timepoints. There were no changes in perceived cognition (P = .560), overall neurocognitive performance (P = .924), or neurocognitive domains (P s > .05) from baseline to 6 months post CAR-T. At 6 months, 32.9% reported improved, 47.1% stable, and 20.0% declined perceived cognition relative to baseline. In unadjusted analyses, progressive disease ( = -8.86, P = .012), baseline elevated C-reactive protein ( = -5.60, P = .076) and baseline neurologic comorbidity ( = -11.4, P = .052) were numerically associated with worse perceived cognition over time. In multivariate analyses, only progressive disease was statistically significantly associated with worse perceived cognition ( = -7.32, P = .032) over time.
We found stable cognition among CAR-T recipients and identified an association of therapy response with change in perceived cognition over time.
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