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NK 细胞在急性髓系白血病中的潜在治疗作用:一项系统综述研究

英文原题:Potential therapeutic roles of natural killer cells in acute myeloid leukemia: a systematic review study.

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Potential therapeutic roles of natural killer cells in acute myeloid leukemia: a systematic review study.

PubMed 2025/07/04(内容时间) Clin Exp Med Q2 · IF 4.5(JCR 2025)

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中文摘要

急性髓系白血病(AML)是一种由造血前体细胞基因突变引起的血液癌症,导致骨髓(BM)中细胞生成异常,并引发贫血、白细胞减少和血小板减少等并发症。化疗和造血干细胞移植等治疗手段存在移植物抗宿主病(GVHD)和因免疫抑制导致的感染等风险。近年来,自然杀伤(NK)细胞治疗已成为治疗AML的一种新方法。NK细胞能够识别并摧毁白血病细胞,NK细胞输注和细胞因子激活等方法显示出作为有效治疗手段的前景。本文评估了基于NK细胞的疗法用于AML患者的可行性和安全性。本文是一项系统综述,其方案已在PROSPERO注册。使用关键词“Natural killer cell”“Acute myeloid leukemia”和“Immunotherapy”在PubMed、Scopus、Google Scholar和Web of Science数据库中进行了策略性检索。

去除重复文献并应用纳入/排除标准后,筛选出1623篇文章。两名评审员筛选了标题和摘要,随后进行了全文审查。分歧由第三名评审员解决,最终纳入17篇文章。数据在Excel中整理,研究质量使用Cochrane偏倚风险工具进行评估。数据分析使用R软件进行。在最初识别的1623条记录中,纳入了17项临床研究,共包含402名AML患者,年龄在1至82岁之间。大多数研究使用异基因或同基因NK细胞,有时联合化疗或白细胞介素-2。汇总完全缓解(CR)率为48.22%(95% CI 31.75-65.09%),存在显著异质性(I 2 = 76%)。14项研究中的免疫反应发生率为69.34%(95% CI 49.18-84.09%)。不良事件总体轻微且可控,未出现一致的重度毒性报告。尽管研究质量参差不齐,但有8项研究显示低偏倚风险。在CR结局方面检测到发表偏倚,校正后CR率调整为36.94%。

我们开展的系统评价表明,NK细胞疗法在治疗AML患者中显示出有前景的疗效和可接受的安全性,合并完全缓解率为48.22%,免疫缓解率令人鼓舞。尽管研究间存在异质性且方法学质量不一,但抗白血病效应的持续观察结果和可控的不良事件支持NK细胞疗法作为辅助治疗的潜在作用。有必要开展进一步高质量、大规模试验以验证这些发现并优化临床方案。

展开英文摘要原文

Acute myeloid leukemia (AML) is a blood cancer caused by genetic mutations in hematopoietic precursor cells, leading to abnormal cell production in the bone marrow (BM) and results in complications like anemia, leukopenia, and thrombocytopenia. Treatments, such as chemotherapy and hematopoietic stem cell transplantation carry risks like graft-versus-host disease (GVHD) and infections due to immune suppression. Recently, treatment with natural killer (NK) cells has emerged as a novel approach for treating AML. NK cells can identify and destroy leukemic cells, and methods like NK cell transfer and cytokine activation show promise as effective treatments. This article evaluates the feasibility and safety of NK cell-based therapies for AML patients. This article is a systematic review that registered its protocol in PROSPERO. A strategic search was conducted in the PubMed, Scopus, Google Scholar, and Web of Science databases using the keywords "Natural killer cell, " "Acute myeloid leukemia" and "Immunotherapy". After removing duplicates and applying inclusion/exclusion criteria, 1623 articles were selected.

Two reviewers screened titles and abstracts, followed by a full-text review. Disagreements were resolved by a third reviewer, resulting in 17 articles for inclusion. Data were organized in Excel, and study quality was assessed using the Cochrane risk-of-bias tool. Data analysis was performed using R software. Out of 1623 initially identified records, 17 clinical studies comprising 402 AML patients aged between 1 and 82 years were included. Most studies used allogeneic or homologous NK cells, sometimes combined with chemotherapy or interleukin-2.

The pooled complete remission (CR) rate was 48. 22% (95% CI 31. 75-65. 09%), with significant heterogeneity (I 2 = 76%). Immune response prevalence across 14 studies was 69. 34% (95% CI 49. 18-84. 09%). Adverse events were generally mild and manageable, with no consistent reports of severe toxicity. Although study quality varied, eight studies demonstrated low risk of bias. Publication bias was detected for CR outcomes, adjusting the CR rate to 36. 94% after correction.

We conducted a systematic review that demonstrates that NK cell therapy shows promising efficacy and acceptable safety in treating AML patients, with a pooled complete remission rate of 48. 22% and encouraging immune response rates. Despite heterogeneity across studies and varying methodological quality, the consistent observation of anti-leukemic effects and manageable adverse events supports the potential role of NK cell therapy as a complementary treatment.

Further high-quality, large-scale trials are warranted to validate these findings and optimize clinical protocols.

论文信息

作者
Khani-Eshratabadi M、Motallebzadeh Khanmiri J、Dashti MR、Esmaeili S、Moradi Sani Z、Daei A、Hedayat Hasanabadi M、Saberi Amarghan S
第一作者单位
Kashmar School of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.Iran
通讯作者单位
Immunology Research Center, Tabriz University of Medical Sciences, Daneshghah Ave, Tabriz, Iran. baradaranb@tbzmed.ac.ir.Iran
文献类型
系统综述
期刊
Clinical and experimental medicine2025 Jul 4
原文标识
PubMed 40613944 · DOI 10.1007/s10238-025-01786-w