Peled Jonathan U, Devlin Sean M, Staffas Anna, Lumish Melissa, Khanin Raya, Littmann Eric R, Ling Lilan, Kosuri Satyajit, Maloy Molly, Slingerland John B, Ahr Katya F, Porosnicu Rodriguez Kori A, Shono Yusuke, Slingerland Ann E, Docampo Melissa D, Sung Anthony D, Weber Daniela, Alousi Amin M, Gyurkocza Boglarka, Ponce Doris M, Barker Juliet N, Perales Miguel-Angel, Giralt Sergio A, Taur Ying, Pamer Eric G, Jenq Robert R, van den Brink Marcel R M
Jonathan U. Peled, Sean M. Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R. Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B. Slingerland, Katya F. Ahr, Kori A. Porosnicu Rodriguez, Yusuke Shono, Ann E. Slingerland, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Memorial Sloan Kettering Cancer Center; Jonathan U. Peled, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Weill Cornell Medical College; Melissa Lumish, New York University Langone Medical Center, New York, NY; Anthony D. Sung, Duke University Medical Center, Durham, NC; Daniela Weber, University Medical Center, Regensburg, Germany; and Amin M. Alousi, University of Texas MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2017 May 20;35(15):1650-1659. doi: 10.1200/JCO.2016.70.3348. Epub 2017 Mar 15.
Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.
目的 异基因造血细胞移植（allo-HCT）后死亡的主要原因是复发、移植物抗宿主病（GVHD）和感染。我们之前报道过，肠道菌群的改变与allo-HCT后的GVHD、菌血症及总生存率降低有关。由于肠道细菌是全身免疫反应（包括抗肿瘤效应）的有力调节因子，我们推测肠道菌群的组成成分可能与allo-HCT后的复发有关。方法 通过对前瞻性收集的粪便样本进行16S核糖体测序，分析了541例接受allo-HCT患者的肠道微生物群。在一项回顾性发现-验证队列研究中，我们使用病因特异性比例风险模型，研究了微生物物种或相关物种组的丰度与allo-HCT后2年随访期内疾病复发/进展之间的关系。结果 在验证集中，主要由黏液真杆菌组成的细菌组丰度较高与疾病复发/进展风险降低相关（风险比[HR]，丰度每增加10倍为0.82；95%CI，0.71至0.95；P = 0.009）。根据该细菌组的有无对患者进行分类时，存在该细菌组也与疾病复发/进展较少相关（HR，0.52；95%CI，0.31至0.87；P = 0.01）。有和没有该细菌组的患者2年复发/进展累积发生率分别为19.8%和33.8%。这些关联在多变量模型中仍然显著，并且在接受富含T细胞同种异体移植物的受者中最强。结论 我们发现肠道菌群中一组细菌的丰度与allo-HCT后疾病的复发/进展之间存在关联。这些可能作为潜在的生物标志物或治疗靶点，以预防复发并提高allo-HCT后的生存率。
