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利用红细胞分布宽度(RDW)作为预测 CAR-T 细胞治疗后疗效的可靠生物标志物

英文原题:Utilizing red blood cell distribution width (RDW) as a reliable biomarker to predict treatment effects after chimeric antigen receptor T cell therapy.

查看英文原题

Utilizing red blood cell distribution width (RDW) as a reliable biomarker to predict treatment effects after chimeric antigen receptor T cell therapy.

PubMed 2024/05/21(内容时间) Clin Exp Med Q2 · IF 4.5(JCR 2025)

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中文摘要

CAR-T 细胞疗法是治疗 B 细胞恶性肿瘤的有效方法。然而,仍有一定比例患者在 CAR-T 治疗后复发;由于难以准确预测复发,需要在输注 CAR-T 前找到能够预测其疗效强度和持续时间的生物标志物。

因此,我们开展单中心队列研究,纳入 91 例接受 CAR-T 治疗的弥漫大 B 细胞淋巴瘤(DLBCL)患者,以识别新的预后标志物。确认既往报告的各项预后参数(白细胞单采时疾病状态、原发难治状态、治疗线数、白细胞单采时 CD3+ 细胞计数)预测能力均有限后,我们整合这四项变量建立新的复合参数,发现其可显著预测 CAR-T 输注后的无进展生存期(PFS)。

此外,通过将该复合参数与所有单项实验室变量进行全面相关性分析,我们发现白细胞单采时红细胞分布宽度标准差(RDW-SD)与该复合参数显著相关,可能是一项预后生物标志物(R² = 0.76,p = 0.02)。验证分析表明,RDW-SD 较高与 CAR-T 治疗后较差的 PFS 显著相关(HR = 3.46,P = 0.03)。

因此,本研究提示,白细胞单采时 RDW-SD 是一种新型且有用的单项生物标志物,可较早获得并用于预测 CAR-T 疗效。对复发风险较高的患者,应考虑采用 CAR-T 后维持治疗或再诱导治疗。

展开英文摘要原文

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion.

Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker.

After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3 + cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance.

Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R 2 = 0. 76, p = 0. 02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3. 46, P = 0. 03).

Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.

论文信息

作者
Nakamura N、Jo T、Arai Y、Kitawaki T、Nishikori M、Mizumoto C、Kanda J、Yamashita K
第一作者单位
Department of Hematology, Kyoto University Hospital, Kyoto, Japan.Japan
通讯作者单位
Department of Hematology, Kyoto University Hospital, Kyoto, Japan. ysykrai@kuhp.kyoto-u.ac.jp.Japan
期刊
Clinical and experimental medicine2024 May 21
原文标识
PubMed 38771501 · DOI 10.1007/s10238-024-01373-5