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急性白血病患者异基因造血干细胞移植后早期循环免疫细胞亚群的预测作用

Predictive Role of Circulating Immune Cell Subtypes Early after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia.

作者信息

Kim Tae Woo, Park Sung-Soo, Lim Ji-Young, Min Gi June, Park Silvia, Jeon Young-Woo, Yahng Seung-Ah, Shin Seung-Hwan, Lee Sung-Eun, Yoon Jae-Ho, Cho Byung-Sik, Eom Ki-Seong, Lee Seok, Kim Hee-Je, Min Chang-Ki

机构信息

Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.

出版信息

Int J Stem Cells. 2018 Dec 31;12(1):73-83. doi: 10.15283/ijsc18094.

Abstract

BACKGROUND AND OBJECTIVES

Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission.

METHODS

Peripheral blood samples were taken at the median of 14 days (range, 12∼29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry.

RESULTS

The median age was 49.0 years (range, 21∼69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8 T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III-IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091∼0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078∼0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III-IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse.

CONCLUSIONS

iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.

摘要

背景与目的

在异基因造血干细胞移植(allo-HSCT)后的最初几周至几个月内,固有免疫细胞通常会恢复。它们在移植物抗宿主病(GVHD)和移植物抗白血病(GVL)效应方面的相关性很大程度上尚不清楚。本研究在首次获得完全缓解的急性白血病患者中,探讨了免疫细胞早期恢复对allo-HSCT后急性GVHD和GVL效应的预测作用。

方法

在allo-HSCT后第14天(范围12~29天)采集外周血样本。对包含119份样本及患者特征的队列进行分析。通过流式细胞术鉴定免疫细胞群体。

结果

移植时的中位年龄为49.0岁(范围21~69岁)。单因素分析显示,年龄小于40岁、CD8 T细胞、不变自然杀伤T(iNKT)细胞、单核细胞源性髓系抑制细胞(M-MDSC)频率较低以及未成熟MDSC频率较高与III-IV级急性GVHD的发生相关。多因素分析显示,iNKT细胞(风险比(HR),0.453,95%置信区间,0.091~0.844,p = 0.024)和M-MDSC(HR,0.271,95%置信区间,0.078~0.937,p = 0.039)是独立因素。两个细胞亚群频率均较高的组合与III-IV级急性GVHD的较低发生率相关,而iNKT细胞频率较低且M-MDSC频率较高的患者复发概率显著更高。

结论

iNKT细胞和M-MDSC可能是预测接受allo-HSCT治疗的急性白血病患者急性GVHD和/或复发的相关细胞生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f83a/6457701/b6ee905e9359/ijsc-12-073f1.jpg

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