PDF(Pubmed)
Abstract：
UNASSIGNED: Transient abnormal myelopoiesis (TAM) occurs in 10% of neonates with Down syndrome (DS). Although most patients show spontaneous resolution of TAM, early death occurs in ∼20% of cases. Therefore, new biomarkers are needed to predict early death and determine therapeutic interventions. This study aimed to determine the association between clinical characteristics and cytokine levels in patients with TAM. A total of 128 patients with DS with TAM enrolled in the TAM-10 study conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group were included in this study. Five cytokine levels (interleukin-1b [IL-1b], IL-1 receptor agonist, IL-6, IL-8, and IL-13) were significantly higher in patients with early death than in those with nonearly death. Cumulative incidence rates (CIRs) of early death were significantly associated with high levels of the 5 cytokines. Based on unsupervised consensus clustering, patients were classified into 3 cytokine groups: hot-1 (n = 37), hot-2 (n = 42), and cold (n = 49). The CIR of early death was significantly different between the cytokine groups (hot-1/2, n = 79; cold, n = 49; hot-1/2 CIR, 16.5% [95% confidence interval (CI), 7.9-24.2]; cold CIR, 2.0% [95% CI, 0.0-5.9]; P = .013). Furthermore, cytokine groups (hot-1/2 vs cold) were independent poor prognostic factors in the multivariable analysis for early death (hazard ratio, 15.53; 95% CI, 1.434-168.3; P = .024). These results provide valuable information that cytokine level measurement was useful in predicting early death in patients with TAM and might help to determine the need for therapeutic interventions. This trial was registered at UMIN Clinical Trials Registry as #UMIN000005418.
摘要：
短暂性异常骨髓生成（TAM）发生在10％的唐氏综合征（DS）新生儿中。虽然大多数患者表现出TAM的自发消退，大约20%的病例发生早期死亡。因此,需要新的生物标志物来预测早期死亡和确定治疗干预措施.本研究旨在确定TAM患者的临床特征与细胞因子水平之间的关系。本研究纳入了由日本小儿白血病/淋巴瘤研究组进行的TAM-10研究中的128例患有TAM的DS患者。五种细胞因子水平[白细胞介素（IL）-1b，IL-1受体激动剂,早期死亡患者的IL-6、IL-8和IL-13]显著高于非早期死亡患者。早期死亡的累积发生率（CIR）与五种细胞因子的高水平显着相关。基于无监督共识聚类，患者分为三个细胞因子组：hot-1(n=37)，hot-2(n=42)，冷（n=49）。早期死亡的CIR在细胞因子组之间存在显着差异[hot-1/2（n=79）;冷（n=49）;CIR（95％置信区间[CI]）=16.5％（7.9％-24.2％）;2.0％（0.0％-5.9％），P=0.013]。此外，细胞因子组（hot-1/2vs.冷）是早期死亡的多变量分析中的独立不良预后因素[风险比（95％CI）=19.25（2.056-180.3），P=0.010]。这些结果提供了有价值的信息，即细胞因子水平测量可用于预测TAM患者的早期死亡，并可能有助于确定治疗干预的必要性。
