Atar Or, Ram Ron, Avivi Irit, Amit Odelia, Vitkon Roy, Luttwak Efrat, Bar-On Yael, Gidron Yori
Department of Nursing, Faculty of Social Welfare and Health Sciences, Haifa University, Haifa 3498838, Israel.
Department of Hematology, Ichilov University Hospital, Tel-Aviv 6423906, Israel.
J Clin Med. 2023 Jan 23;12(3):908. doi: 10.3390/jcm12030908.
This study examined the prognostic role of vagal nerve activity in patients with relapsed/refractory diffused large B-cell lymphoma (R/R-DLBCL) treated with chimeric antigen receptor cell therapy (CAR-T) and in patients with multiple myeloma (MM) undergoing an autologous hematopoietic cell transplantation (AutoHCT). Participants included 29 patients with R/R-DLBCL and 37 patients with MM. Inclusion criteria were: (1) age over 18; (2) diagnosed with DLBCL or MM; (3) being treated with CAR-T or AutoHCT; and (4) having an ECG prior to cell transfusion. The predictor was vagal nerve activity indexed by heart rate variability (HRV) and obtained retroactively from 10 s ECGs. The main endpoint for R/R-DLBCL was overall survival (OS), and for MM the endpoint was progression-free survival (PFS). Data of 122 patients were obtained, 66 of whom were included in the study. In DLBCL, HRV significantly predicted OS independently of confounders (e.g., performance status, disease status at cell therapy), hazard ratio (HR), and 95% confidence interval (HR = 0.20; 95%CI: 0.06-0.69). The prognostic role of disease severity was moderated by HRV: among severely disease patients, 100% died with low HRV, while only 37.5% died with high HRV. In MM, HRV significantly predicted PFS (HR = 0.19; 95%CI: 0.04-0.90) independently of confounders. Vagal nerve activity independently predicts prognosis in patients with R/R-DLBCL and with MM undergoing cell therapy. High vagal activity overrides the prognostic role of disease severity. Testing the effects of vagal nerve activation on prognosis in blood cancers is recommended.
本研究探讨了迷走神经活动在接受嵌合抗原受体细胞疗法（CAR-T）治疗的复发/难治性弥漫性大B细胞淋巴瘤（R/R-DLBCL）患者以及接受自体造血细胞移植（AutoHCT）的多发性骨髓瘤（MM）患者中的预后作用。参与者包括29例R/R-DLBCL患者和37例MM患者。纳入标准为：（1）年龄超过18岁；（2）诊断为DLBCL或MM；（3）接受CAR-T或AutoHCT治疗；（4）在细胞输注前进行过心电图检查。预测指标是通过心率变异性（HRV）索引的迷走神经活动，并从10秒心电图中追溯获取。R/R-DLBCL的主要终点是总生存期（OS），MM的终点是无进展生存期（PFS）。获取了122例患者的数据，其中66例纳入研究。在DLBCL中，HRV显著独立于混杂因素（如体能状态、细胞治疗时的疾病状态）预测OS，危险比（HR）及95%置信区间（HR = 0.20；95%CI：0.06 - 0.69）。疾病严重程度的预后作用受HRV调节：在疾病严重的患者中，HRV低者100%死亡，而HRV高者仅37.5%死亡。在MM中，HRV显著独立于混杂因素预测PFS（HR = 0.19；95%CI：0.04 - 0.90）。迷走神经活动独立预测R/R-DLBCL患者及接受细胞治疗的MM患者的预后。高迷走神经活动超越了疾病严重程度的预后作用。建议测试迷走神经激活对血液系统恶性肿瘤预后的影响。
