Universite Lille Nord de France, Lille, France.
Bone Marrow Transplant. 2010 Oct;45(10):1546-52. doi: 10.1038/bmt.2010.13. Epub 2010 Mar 1.
T-cell reconstitution after allo-SCT initially depends on homeostatic peripheral expansion of donor T cells, the level of which may promote the differentiation of alloreactive and tumor-reactive effectors. IL-7 and IL-15 exert their effect as key homeostatic cytokines. We prospectively investigated plasma levels of IL-7 and IL-15 in a homogeneous group of 40 patients in CR of their hematologic malignancy undergoing myeloablative, fully (10/10) HLA-matched BMT. IL-7 and IL-15 proceeded along similar kinetic courses, peaking at wide ranges (3.8-30.2 and 14.3-66 pg/ml, respectively) on day +14 when all patients were profoundly lymphopenic. Occurrence and grade of subsequent acute GVHD were significantly associated with heightened day +14 IL-7 and IL-15 levels. Association of peak IL-7 level to grade 2-4 acute GVHD was confirmed by Cox multivariate analysis (hazard ratio (HR)=5.38; P=0.022). Malignancy relapse was significantly associated with reduced day +14 levels of IL-15 (Cox multivariate analysis: HR=0.93; P=0.035). Plasma IL-7 and IL-15 levels in the early post transplantation period are therefore biomarkers that can help predict subsequent development of acute GVHD and malignancy relapse.
T 细胞在异基因 SCT 后最初的重建依赖于供体 T 细胞的稳态外周扩增,其水平可能促进同种反应性和肿瘤反应性效应物的分化。IL-7 和 IL-15 作为关键的稳态细胞因子发挥作用。我们前瞻性地研究了 40 例血液恶性肿瘤患者在接受清髓性、完全(10/10)HLA 匹配 BMT 后处于缓解期的血浆中 IL-7 和 IL-15 的水平。IL-7 和 IL-15 呈现相似的动力学过程,在第 +14 天达到高峰,范围广泛(分别为 3.8-30.2 和 14.3-66pg/ml),此时所有患者均严重淋巴细胞减少。随后发生急性 GVHD 的程度与第 +14 天升高的 IL-7 和 IL-15 水平显著相关。Cox 多因素分析证实,峰值 IL-7 水平与 2-4 级急性 GVHD 相关(风险比(HR)=5.38;P=0.022)。恶性肿瘤复发与第 +14 天 IL-15 水平降低显著相关(Cox 多因素分析:HR=0.93;P=0.035)。因此,移植后早期的血浆 IL-7 和 IL-15 水平是可以帮助预测随后发生急性 GVHD 和恶性肿瘤复发的生物标志物。