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经颅多普勒作为 CAR-T 细胞相关神经毒性生物标志物的应用

英文原题:Use of Transcranial Doppler as a Biomarker of CAR T Cell-Related Neurotoxicity.

查看英文原题

Use of Transcranial Doppler as a Biomarker of CAR T Cell-Related Neurotoxicity.

PubMed 2022/02/01(内容时间) Neurol Clin Pract Q2 · IF 3.7(JCR 2025)

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研究概要

我们的研究表明,TCD MFV 升高与神经毒性的发生及神经毒性发作时间存在关联。我们认为,TCD 超声可作为 CAR-T 细胞患者的床旁功能生物标志物,并可能指导免疫干预措施,以管理这一复杂患者群体中的毒性。

研究思路结论见上方概要

探讨经颅多普勒(TCD)平均血流速度(MFV)与复发性淋巴瘤患者接受嵌合抗原受体(CAR)T细胞治疗后神经毒性的严重程度及发生时间之间的关系。

我们确定了165例接受CAR-T 细胞治疗的复发/难治性B细胞淋巴瘤患者队列。TCD在基线、治疗第5天以及整个住院期间根据神经系统症状的出现进行。我们评估了6条主要幕上动脉中每条动脉速度相对于基线的百分比变化,以及这些数值与神经毒性发生及发生时间的关系。

我们的队列中女性占30%,平均年龄为60岁。在接受TCD检查的患者中,63%发生了神经毒性,32%发生了严重神经毒性。神经毒性发生的中位时间为第7天。所有血管中MFV最大百分比变化越高,与发生神经毒性的可能性显著相关(p = 0.0002),并与严重神经毒性相关(p = 0.0421)。我们发现,随着MFV百分比变化的增加,TCD速度变化日与神经毒性发生日之间的相关性强度增加。没有任何单一血管中MFV的增加与神经毒性相关。

展开英文摘要原文

We identified a cohort of 165 patients with relapsed or refractory B-cell lymphoma who received CAR T-cell therapy. TCDs were performed at baseline, treatment day 5, and throughout hospitalization based on development of neurologic symptoms. We assessed the percent change in velocity from baseline in each of the 6 major supratentorial arteries and the relationship of these values to development and timing of neurotoxicity.

Our cohort was 30% female with an average age of 60 years. Of patients with TCDs performed, 63% developed neurotoxicity, and 32% had severe neurotoxicity. The median time of neurotoxicity onset was day 7. Higher maximum percent change in MFV across all vessels was significantly associated with likelihood of developing neurotoxicity ( p = 0.0002) and associated with severe neurotoxicity ( p = 0.0421). We found that with increased percent change in MFV, the strength of correlation between day of TCD velocity change and day of neurotoxicity onset increased. There was no single vessel in which increase in MFV was associated with neurotoxicity. DISCUSSION: Our study demonstrates an association between increase in TCD MFV and the development of neurotoxicity, as well as timing of neurotoxicity onset. We believe that TCD ultrasound may be used as a bedside functional biomarker in CAR T-cell patients and may guide immunologic interventions to manage toxicity in this complex patient group.

论文信息

作者
Holroyd KB、Rubin DB、LaRose S、Monk A、Nikiforow S、Jacobson C、Vaitkevicius H
单位
Department of Neurology (KBH, SL, AM, HV), Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Neurology (DBR), Massachusetts General Hospital, Harvard Medical School, Boston; and Department of Medical Oncology (SN, CJ), Dana Farber Cancer Institute, Harvard Medical School, Boston, MA.United States
期刊
Neurology. Clinical practice2022 Feb
原文标识
PubMed 36157627 · DOI 10.1212/CPJ.0000000000001130