Natural Killer Cell Immunotherapy After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia Patients: Phase I Clinical Trial.

IF 4.9 3区医学 Q2 CELL & TISSUE ENGINEERING

Stem Cell Reviews and Reports Pub Date : 2026-10-01 Epub Date: 2026-08-03 DOI:10.1007/s12015-026-11193-7

Shiva Eskandarian, Amirhossein Izadpanah, Saye Parkhideh, Mahshid Mehdizade, Sahar Parkhideh, Mozhdeh Mohammadian, Mehrshad Seresht-Ahmadi, Mehdi Bakhtiyaridovvombaygi, Abdollah Sabri, Ahmad Gharehbaghian, Abbas Hajifathali, Elham Roshandel

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引用次数: 0

Abstract

Background: Immunotherapy offers a promising approach to prevent relapse and transplant complications. Natural killer (NK) cells play a crucial role in the immune system's initial defense against infections and malignant cells. Activation of NK cells with interleukin-15 enhances anti-leukemic immune responses. We conducted this clinical trial to evaluate the safety and efficacy of CD56 + cell infusion in increasing survival and reducing relapse in patients with acute myeloid leukemia.

Methods: Three escalating doses of 1 × 10⁶, 3 × 10⁶, and 5 × 10⁶ interleukin-15-activated CD56 + cells/kg derived from peripheral blood of haploidentical donors were injected on days + 7, +14, and + 21 following transplantation. Patients were monitored for adverse events. To evaluate efficacy, bone marrow samples were taken on days + 30 and + 90. On day + 40, the population of NK cells and its correlation with patients' clinical status were evaluated. Besides, immune reconstitution was examined on day + 40. Patients were followed up for one year.

Results: The CD56 + cells infusion was safe and not associated with any complications. While survival rates were not statistically different between the intervention and control groups, a trend toward improved survival was observed in the intervention group. Patients with complete remission showed a higher percentage of NK cells on day + 40 than patients who experienced graft rejection, relapse, or death.

Conclusions: In this study, we introduce a feasible method for activating CD56 + cells. Although the survival rates of patients in the intervention and control groups did not differ statistically, this study showed that a higher percentage of NK cells on day + 40 is associated with better survival and fewer complications following transplantation.

Trial registration: This study was registered at the Iranian Registry of Clinical Trials under code IRCT20230801058996N2 on 2023-09-10.

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急性白血病患者同种异体造血干细胞移植后的自然杀伤细胞免疫治疗：I期临床试验。

背景：免疫治疗为预防复发和移植并发症提供了一种很有前途的方法。自然杀伤细胞（NK）在免疫系统对感染和恶性细胞的初始防御中起着至关重要的作用。白细胞介素-15激活NK细胞增强抗白血病免疫反应。我们进行了这项临床试验，以评估CD56 +细胞输注在提高急性髓性白血病患者生存率和减少复发方面的安全性和有效性。方法：在移植后+ 7、+14和+ 21天，分别以1 × 106、3 × 106和5 × 106白介素-15活化CD56 +细胞/kg的剂量递增注射单倍体供者外周血。监测患者的不良事件。为了评估疗效，在+ 30和+ 90天采集骨髓样本。第40天，评估NK细胞数量及其与患者临床状况的相关性。第40天检测免疫重建。患者随访1年。结果：CD56 +细胞输注安全，无并发症发生。虽然存活率在干预组和对照组之间没有统计学差异，但在干预组中观察到生存率有改善的趋势。完全缓解的患者在第40天的NK细胞百分比高于经历移植排斥、复发或死亡的患者。结论：本研究为CD56 +细胞的激活提供了一种可行的方法。虽然干预组和对照组患者的生存率没有统计学差异，但本研究表明，第40天NK细胞百分比较高与移植后生存率较高和并发症较少相关。试验注册：本研究已于2023-09-10在伊朗临床试验注册中心注册，代码为IRCT20230801058996N2。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reviews and Reports 医学-细胞生物学

CiteScore

9.30

自引率

4.20%

发文量

审稿时长

3 months

期刊介绍： The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.