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细胞因子谱与 B 细胞成熟抗原靶向 CAR-T 细胞治疗后的持续性血液学毒性相关

英文原题:Cytokine profiles are associated with prolonged hematologic toxicities after B-cell maturation antigen targeted chimeric antigen receptor-T-cell therapy.

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Cytokine profiles are associated with prolonged hematologic toxicities after B-cell maturation antigen targeted chimeric antigen receptor-T-cell therapy.

PubMed 2022/12/07(内容时间) Cytotherapy Q1 · IF 4.5(JCR 2025)

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研究概要

我们的发现增进了对细胞因子影响造血功能的理解,这可能有助于机制研究和潜在干预策略的探索。

研究思路结论见上方概要

B细胞成熟抗原靶向嵌合抗原受体(CAR)-T细胞疗法在复发/难治性多发性骨髓瘤治疗中的显著疗效已被广泛证实。然而,在临床实践中,延长的血液学毒性(PHT)延长了住院时间并损害了长期生存。

这项回顾性研究回顾了2018年4月至2021年9月期间在我院接受B细胞成熟抗原CAR-T 细胞治疗的99例复发/难治性多发性骨髓瘤患者(ChiCTR1800017404)。

在93例可评估患者中,CAR-T 细胞输注后长期血液学毒性的发生率较高,包括38.71%(36/93)的患者出现长期中性粒细胞减少,22.58%(21/93)出现长期贫血,59.14%(55/93)出现长期血小板减少。此外,9.68%(9/93)的患者出现长期全血细胞减少。我们的多因素分析确定,细胞因子谱是PHTs的独立危险因素,而充足的基线造血功能和CAR-T 细胞的高CD4/CD8比值是CAR-T 细胞输注后PHTs的保护因素。亚组分析发现,CAR-T 后血液学参数的动力学主要由细胞因子释放综合征和基线造血功能的共同效应决定,并显示出对三个谱系的影响权重。

展开英文摘要原文

This retrospective study reviewed 99 patients with relapsed or refractory multiple myeloma who underwent B-cell maturation antigen CAR-T-cell therapy at our institution between April 2018 and September 2021 (ChiCTR1800017404).

Among 93 evaluable patients, the incidence of prolonged hematologic toxicities was high after CAR-T-cell infusion, including 38.71% (36/93) of patients with prolonged neutropenia, 22.58% (21/93) with prolonged anemia and 59.14% (55/93) with prolonged thrombocytopenia. In addition, 9.68% (9/93) of patients experienced prolonged pancytopenia. Our multivariate analyses identified that cytokine profiles were independent risk factors for PHTs, whereas a sufficient baseline hematopoietic function and high CD4/CD8 ratio of CAR-T cells were protective factors for PHTs after CAR-T-cell infusion. Subgroup analyses found that the kinetics of post-CAR-T hematologic parameters were primarily determined by the collective effects of cytokine release syndrome and baseline hematopoietic functions, and showed influential weights for the three lineages.

Our findings improve the understanding of the impact of cytokines on hematopoietic functions, which could contribute to the mechanism investigation and exploration of potential intervention strategies.

论文信息

作者
Wang L、Hong R、Zhou L、Wang Y、Lv Y、Ni F、Zhang M、Zhao H
第一作者单位
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;; Institute of Hematology, Zhejiang University, Hangzhou, China;; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China.China
通讯作者单位
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China;; Institute of Hematology, Zhejiang University, Hangzhou, China;; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China. Electronic address: huanghe@zju.edu.cn.China
期刊
Cytotherapy2023 Feb
原文标识
PubMed 36496302 · DOI 10.1016/j.jcyt.2022.11.001