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第90天时自然杀伤细胞计数高预示着T细胞去除的异基因干细胞移植后无事件患者的生存率提高。

High NK cell counts at day 90 predict improved survival in event-free patients after T-cell depleted allogeneic stem cell transplantation.

作者信息

Pešić Andrej, Bešević Nevena, Kröger Nicolaus, Stanisavljević Dejana, Kraguljac Kurtović Nada, Bukumirić Zoran, Kecman Natalija, Lemajić Nikola, Smiljanić Mihailo, Suvajdžić Vuković Nada, Bogdanović Andrija, Vidović Ana, Bila Jelena, Mitrović Mirjana, Leković Danijela, Virijević Marijana, Đunić Irena, Antić Darko, Todorović Balint Milena

机构信息

Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia.

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Front Immunol. 2025 Jun 18;16:1577924. doi: 10.3389/fimmu.2025.1577924. eCollection 2025.

Abstract

INTRODUCTION

Immune reconstitution (IR) after allogeneic stem cell transplantation has been highlighted as pivotal in achieving favorable long-term outcomes by influencing the rates of infection, graft versus host disease (GvHD) and relapse. However, data on the impact of different lymphocyte subsets influencing outcomes is conflicting. Furthermore, the importance of immune reconstitution parameters in patients previously not experiencing major post-transplant complications is lacking.

METHODS

We evaluated the clinical impact of day 90 NK cell, CD4 T-cell, CD8 T-cell, B-cell, and NKT cell counts on transplant outcomes by performing a landmark analysis in event-free patients. Lymphocyte subset counts were obtained from 70 patients undergoing in vivo T-cell depleted allogeneic transplantation from 2018 to 2024. Patients eligible for the study experienced no acute GvHD, poor graft function, graft failure, or relapse in the first three months after transplantation-prior to obtaining IR data. We associated lymphocyte subset counts to overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse (RI), and secondary graft failure/poor graft function.

RESULTS

High NK cell counts on day 90 (>178/μL) were associated with improved OS (P=0.039) and lower rates of NRM (1-year cumulative incidence of 5.7% versus 31.4%, HR 0.16, 95% CI 0.04-0.69, P=0.014). A protective effect on RI was not found. We found no patient, disease or transplant-related variables to be significantly associated with day 90 NK cell counts.

CONCLUSION

The results suggest that high NK cell counts on day 90 after T-cell depleted allogeneic transplantation independently protect from NRM and improve OS in patients without prior major post-transplant complications.

摘要

引言

异基因干细胞移植后的免疫重建(IR)已被视为通过影响感染率、移植物抗宿主病(GvHD)和复发率来实现良好长期预后的关键因素。然而,关于不同淋巴细胞亚群对预后影响的数据存在冲突。此外,此前未经历重大移植后并发症的患者中免疫重建参数的重要性尚不明确。

方法

我们通过对无事件患者进行标志性分析,评估了第90天自然杀伤(NK)细胞、CD4 T细胞、CD8 T细胞、B细胞和自然杀伤T(NKT)细胞计数对移植预后的临床影响。淋巴细胞亚群计数来自2018年至2024年接受体内T细胞去除的异基因移植的70例患者。在获得免疫重建数据之前,符合研究条件的患者在移植后的前三个月未发生急性GvHD、移植物功能不良、移植物失败或复发。我们将淋巴细胞亚群计数与总生存期(OS)、非复发死亡率(NRM)、累积复发率(RI)以及继发性移植物失败/移植物功能不良相关联。

结果

第90天NK细胞计数高(>178/μL)与OS改善相关(P=0.039),且NRM率较低(1年累积发病率分别为5.7%和31.4%,HR 0.16,95%CI 0.04 - 0.69,P=0.014)。未发现对RI有保护作用。我们未发现患者、疾病或移植相关变量与第90天NK细胞计数有显著关联。

结论

结果表明,T细胞去除的异基因移植后第90天NK细胞计数高可独立保护无先前重大移植后并发症的患者免受NRM影响并改善OS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd00/12213383/5aafb8a5509a/fimmu-16-1577924-g001.jpg

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