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淋巴瘤嵌合抗原受体 T 细胞治疗后患者认知变化。

Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma.

机构信息

Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida.

Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida.

出版信息

Transplant Cell Ther. 2022 Jul;28(7):401.e1-401.e7. doi: 10.1016/j.jtct.2022.05.015. Epub 2022 May 14.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. This study examined changes in cognition in the first year after CD19-directed CAR T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.g., ICANS, CRS) and nonspecific risk factors (e.g., baseline quality of life, frailty) for worsening cognition. Patients' perceived cognition was assessed at baseline and at days 90 and 360. Clinical variables were abstracted from medical records. Piecewise mixed models were used to examine acute change (i.e., within 90 days) and longer-term change (i.e., from 90 days to 360 days) in cognition, as well as to explore risk factors for worsening cognition. Among 118 participants (mean age 61, 59% male), mean levels of perceived cognition did not change from baseline to day 90 (P> .05) but worsened from day 90 to day 360 in global cognition and in the domains of memory, language, organization, and divided attention (P< .05). Although statistically significant, changes were small (d values 0.15-0.28). Greater baseline fatigue, anxiety, and depression were associated with worse global cognition at day 90 (P< .01). Patients with more severe ICANS post-CART reported worse global cognition at day 360 (P< .05), although there were no differences in perceived cognition by severity of CRS (P> .05). Other putative risk factors were not associated with acute or longer-term changes in perceived cognition (P> .05). CAR T-cell therapy recipients reported delayed deterioration in several cognitive domains, although changes were small. These findings may be useful when educating future patients on what to expect when receiving CAR T-cell therapy.

摘要

嵌合抗原受体 (CAR) T 细胞疗法可使复发/难治性血液系统恶性肿瘤患者获得持久缓解。免疫效应细胞相关神经毒性综合征 (ICANS) 和细胞因子释放综合征 (CRS) 较为常见,可能使患者面临长期认知障碍的风险。本研究调查了 CD19 定向 CAR T 细胞治疗淋巴瘤后一年内的认知变化,以及 CAR T 细胞治疗特有的风险因素(如 ICANS、CRS)和非特异性风险因素(如基线生活质量、脆弱性)对认知恶化的影响。患者的认知感知在基线时以及 90 天和 360 天进行评估。临床变量从病历中提取。分段混合模型用于检查认知的急性变化(即 90 天内)和长期变化(即从 90 天到 360 天),并探索认知恶化的风险因素。在 118 名参与者(平均年龄 61 岁,59%为男性)中,认知感知的平均水平从基线到第 90 天没有变化(P>.05),但从第 90 天到第 360 天,在整体认知和记忆、语言、组织和注意力分散领域恶化(P<.05)。尽管有统计学意义,但变化很小(d 值为 0.15-0.28)。基线时疲劳、焦虑和抑郁程度较高与第 90 天的整体认知较差相关(P<.01)。CAR T 细胞治疗后出现更严重的 ICANS 的患者在第 360 天的整体认知更差(P<.05),但 CRS 严重程度对认知感知没有差异(P>.05)。其他潜在的风险因素与感知认知的急性或长期变化无关(P>.05)。CAR T 细胞治疗的接受者报告说,在几个认知领域的认知功能出现延迟恶化,尽管变化很小。这些发现可能在向未来的患者介绍接受 CAR T 细胞治疗时的预期时有用。

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