Suppression of Hematopoietic Primitive Cells in Patients with Secondary Failure of Platelet Recovery after Acute Graft-versus-Host Disease

Aijie Huang, Xiaoming Zhao, Meizhang Li, Gusheng Tang, Yang Fei, Roujia Wang, Lei Gao, Xiong Ni, Weiping Zhang, Jianmin Yang, Xiaoxia Hu, Jianmin Wang
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引用次数: 4

Abstract

Secondary failure of platelet recovery (SFPR) can occur after allogeneic hematopoietic stem cell transplantation (alloHSCT), and 20% of cases are related to acute graft-versus-host disease (aGVHD). The underlying mechanisms of this association are unclear, however. The aim of the present study was to investigate the potential mechanisms of SFPR secondary to aGVHD, which may provide a new therapeutic strategy for these patients. A total of 468 patients with malignant hematologic disease who underwent alloHSCT were included. Sixty-six patients developed SFPR after alloHSCT, and in 45 of these 66 patients (68.2%), SFPR was secondary to grade II-IV aGVHD (SFPR/aGVHD). Compared with patients with good graft function (GGF), patients with SFPR had poor overall survival (20.72% versus 88.01%; P < .0001). Grade II-IV aGVHD was identified as an independent risk factor for SFPR in multivariate analysis (hazard ratio, 9.512; P < .0001). We observed reduced erythroid and megakaryocyte colony formation in bone marrow (BM) samples isolated from SFPR/aGVHD patients, consistent with the lower frequency of megakaryocyte and erythrocyte progenitors in BM. Levels of the inflammatory cytokines IL-2R and TNF-R1 were significantly higher in the SFPR/aGVHD group compared with the GGF group (P = .002 and .001, respectively), as were the frequencies of proinflammatory T helper subsets. Furthermore, the pathways that regulate hematopoiesis and immune responses were universally underexpressed in CD34+ cells isolated from SFPR/aGVHD patients. Differentially expressed genes were significantly enriched in the hematopoietic cell lineage pathway and other pathways involved in both immune responses and megakaryopoiesis. In summary, we found that both the immune microenvironment and compromised proliferation of hematopoietic primitive cells contribute to the development of SFPR secondary to aGVHD, and our data provide new insight into the mechanisms of SFPR in the context of aGVHD.

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急性移植物抗宿主病后继发性血小板恢复失败患者的造血原始细胞抑制
同种异体造血干细胞移植(alloHSCT)后可发生继发性血小板恢复失败(SFPR), 20%的病例与急性移植物抗宿主病(aGVHD)有关。然而,这种关联的潜在机制尚不清楚。本研究旨在探讨aGVHD继发SFPR的潜在机制,为这些患者提供新的治疗策略。共纳入468例接受同种异体造血干细胞移植的恶性血液病患者。66例患者在同种异体移植后发生SFPR,其中45例(68.2%)SFPR继发于II-IV级aGVHD (SFPR/aGVHD)。与移植物功能良好的患者(GGF)相比,SFPR患者的总生存率较差(20.72% vs 88.01%;P & lt;。)。在多因素分析中,II-IV级aGVHD被确定为SFPR的独立危险因素(风险比,9.512;P & lt;。)。我们观察到SFPR/aGVHD患者骨髓(BM)样品中红细胞和巨核细胞集落形成减少,与BM中巨核细胞和红细胞祖细胞频率降低一致。与GGF组相比,SFPR/aGVHD组的炎症细胞因子IL-2R和TNF-R1水平显著升高(P分别为0.002和0.001),促炎T辅助亚群的频率也显著升高。此外,从SFPR/aGVHD患者分离的CD34+细胞中,调节造血和免疫反应的途径普遍表达不足。差异表达基因在造血细胞谱系途径和其他涉及免疫反应和巨核生成的途径中显著富集。综上所述,我们发现免疫微环境和造血原始细胞增殖受损都有助于aGVHD继发性SFPR的发展,我们的数据为aGVHD背景下SFPR的机制提供了新的见解。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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