小儿顽固性/复发性脑肿瘤多次鞘内注射同种异体NK细胞的安全性和可行性。

IF 3.4 2区 医学 Q2 ONCOLOGY
Hamid Mahdizadeh, Amirhossein Izadpanah, Yasaman Nouri, Parisa Shams, Delbar Daneshjou, Alireza Aziz Ahari, Alireza Tabibkhooei, Hamidreza Haghighatkhah, Massoud Vosough, Pooya Faranoush, Masoumeh Azimi, Saba Yousefi, Atefeh Barzegari, Alireza Khosravani, Niloufar Shayan Asl, Mohammad Faranoush, Marzieh Ebrahimi
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引用次数: 0

摘要

背景:小儿胶质瘤是一种罕见的疾病,由于其高复发率,可导致显著的死亡率和发病率。本研究是一项I期非随机临床试验,旨在评估鞘内注射多剂量同种异体NK细胞治疗难治性/复发性胶质瘤的安全性、可行性和潜在疗效。方法:采用CD56 +细胞阳性选择方法,从随机无亲缘关系的健康供体中分离同种异体NK细胞。根据纳入标准选择9例患者,每周接受最多10次5 × 107 NK细胞/次注射。不良事件分级是根据不良事件通用术语标准(CTCAE)检查表进行的。在18个月的随访中,肿瘤大小、脊柱扩散程度和复发时间被认为是疗效的组成部分。此外,回顾性选择6例接受常规治疗的患者。结果:脊髓鞘内多次注射同种异体NK细胞治疗小儿胶质瘤是安全的,无严重不良事件(SAEs)。最常见的ae是头痛[29%(17% 1级和13% 2级)]、发热和发冷[21%(17% 1级和4% 2级)]、呕吐[13% 2级]和背痛[12%(4% 1级和8% 2级)]。在18个月的随访中,干预组中仍存活的5例患者(2024年8月7日)中,3例病情稳定(SD), 1例病情进展(PD), 1例部分缓解(PR),肿瘤大小减小。4例死亡患者中,2例因肿瘤进展死亡,2例因感染死亡。在回顾性对照组中,6例患者中有5例发展为PD和轻脑膜扩散(LMS),其中4例死亡,1例患者显示完全缓解(CR)的放射学证据。脑脊液(CSF)分析显示NK细胞和T细胞百分比增加,IFN-γ和TNF-α水平显著降低。结论:在难治性/复发性胶质瘤患儿中,多次鞘内注射同种异体NK细胞是安全可行的。虽然我们报道了复发发作的减少和总生存率的增加,但需要进一步的研究,延长随访期和适当的对照组,以评估NK细胞治疗对这些患者的疗效。试验注册:该试验已在伊朗临床试验注册中心(IRCT20170122032121N6)注册,日期20121-11-19。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The safety and feasibility of multiple intrathecal injections of allogenic NK cells in pediatrics with refractory/recurrent brain tumors.

Background: Pediatric glioma is a rare condition that can lead to significant mortality and morbidity due to its high recurrence rate. This study is a phase I nonrandomized clinical trial that was conducted to assess the safety, feasibility, and potential efficacy of the intrathecal (IT) injection of multiple doses of allogenic NK cells in pediatric patients with refractory/recurrent gliomas.

Methods: Allogeneic NK cells were isolated from random healthy unrelated donors via positive selection of CD56 + cells. Nine patients were selected according to the inclusion criteria and received weekly doses of up to 10 doses of 5 × 107 NK cells/injection. Adverse events grading was done based on Common Terminology Criteria for Adverse Events (CTCAE) Check lists. The size of the tumor, degree of spinal spreading and duration of relapse during 18 month followup were considered components of efficacy. Additionally, six patients who received conventional treatment were selected retrospectively.

Results: Multiple intrathecal injections of allogeneic NK cells in pediatric gliomas were safe, without any serious adverse events (SAEs). The most prevalent AEs were headache [29% (17% grade 1 and 13% grade 2)], fever and chills [21% (17% grade 1 and 4% grade 2)], vomiting [13% grade 2], and back pain [12% (4% grade 1 and 8% grade 2)]. 18 months of follow-up, among the five patients in the intervention group who were still alive (August 7, 2024), three exhibited stable disease (SD), one had progressive disease (PD), and one experienced a partial response (PR) with a reduction in tumor size. Among the four deceased patients, two died due to tumor progression, and two died due to infections. In the retrospective control group, five out of six patients developed PD and leptomeningeal spread (LMS), four of whom died, and one patient showed radiological evidence of a complete response (CR). Cerebrospinal fluid (CSF) analysis revealed increases in the percentages of NK and T cells and significant reductions in the levels of IFN-γ and TNF-α.

Conclusions: Multiple intrathecal injections of allogeneic NK cells are safe and feasible in pediatric patients with refractory/recurrent gliomas. Although we reported a reduction in recurrence episodes and an increase in overall survival, further studies with extended follow-up periods and appropriate control groups are necessary to assess the efficacy of NK cell therapy in these patients.

Trial registration: The trial was registered on the Iranian Registry of Clinical Trials (IRCT20170122032121N6), Date 2021-11-19.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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