Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Nantes, France; Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; INSERM, UMR1064-Center for Research in Transplantation and Immunology, Nantes, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;
Centre de Recherche Saint-Antoine, INSERM, Unité Mixte de Recherche (UMR) 938, Paris, France; Université Pierre et Marie Curie, Paris, France; Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;
Blood. 2016 Apr 7;127(14):1828-35. doi: 10.1182/blood-2015-12-688739. Epub 2016 Feb 22.
We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.
我们研究了一组包含在粒细胞集落刺激因子动员的外周血干细胞移植物中的免疫细胞(幼稚和记忆 T 细胞亚群、B 细胞、调节性 T 细胞、固有自然杀伤 T 细胞[iNKTs]、NK 细胞和树突状细胞亚群)对接受异基因干细胞移植(SCT)的患者(n=80)的影响,将移植物抗宿主病(GVHD)无和无进展生存(GPFS)的复合终点作为主要终点。我们观察到接受 iNKT 剂量高于和低于中位数的患者的 GPFS 发生率分别为 49%和 22%(P=.007)。在多变量分析中,iNKT 剂量是唯一对 GPFS 有显著影响的参数(风险比=0.48;95%置信区间,0.27-0.85;P=.01)。严重的 III 级至 IV 级急性 GVHD 和美国国立卫生研究院 2 级至 3 级慢性 GVHD 的发生率较低(分别为 12%和 16%),并且与 91%的患者使用抗胸腺细胞球蛋白有关。根据 iNKT 剂量,GVHD 的发生率没有差异。总之,移植物中更高剂量的 iNKTs 与改善 GPFS 相关。这些数据可能为旨在操纵移植物内容以改善同种异体 SCT 结果的前瞻性和主动干预铺平道路。