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