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微生物群作为异基因造血细胞移植患者死亡率的预测因素
Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation


Jonathan U. Peled ... 肿瘤 • 2020.02.27
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摘要


背景

单中心研究已经描述了微生物群的构成与异基因造血细胞移植后的临床结局之间的关联。由于人类微生物群落的构成存在地理差异,并且各机构的临床实践也存在差异,因此提出了上述关联是否具有普遍适用性这一问题。

 

方法

我们利用16S核蛋白体RNA基因测序方法确定了在四个研究中心接受异基因造血细胞移植的患者粪便样本内的微生物群构成情况。在一项观察性研究中,我们利用Cox比例风险分析方法研究了微生物群多样性和死亡率之间的关联。我们使用在纽约研究中心观察到的中位多样性值将研究队列分层,分成高度多样性组和低度多样性组。在对独立队列进行的分析中,纽约研究中心为队列1,德国、日本和美国北卡罗来纳州的三个研究中心构成了队列2。我们对队列1和其中各亚组的其他结局(包括移植相关性死亡)进行了分析。

 

结果

我们对在四个研究中心接受异基因造血细胞移植的1,362例患者的8,767份粪便样本进行了检测。观察到以多样性丧失和单一类群占优势为特征的微生物群破坏模式。在独立队列中,较高的肠道微生物群多样性与较低的死亡风险相关(队列1:高度多样性组354例患者中有104例死亡vs.低度多样性组350例患者中有136例死亡;校正风险比,0.71;95%置信区间[CI],0.55~0.92;队列2:高度多样性组87例患者中有18例死亡vs.低度多样性组92例患者中有35例死亡;校正风险比,0.49;95% CI,0.27~0.90)。亚组分析发现,较低的肠道微生物群多样性与较高的移植相关性死亡和移植物抗宿主病死亡风险相关。移植前采集的基线样本已经显示出微生物群破坏的证据,此外移植前较低的微生物群多样性与较差的生存结局相关。

 

结论

在各移植中心和各地理位置,异基因造血细胞移植期间的微生物群破坏模式相似;微生物群破坏模式的特征是多样性丧失和单一类群占优势。中性粒细胞植入时较高的肠道微生物群多样性与较低的死亡率相关(由美国国立癌症研究所[National Cancer Institute]等资助)。





作者信息

Jonathan U. Peled, M.D., Ph.D., Antonio L.C. Gomes, Ph.D., Sean M. Devlin, Ph.D., Eric R. Littmann, B.A., Ying Taur, M.D., Anthony D. Sung, M.D., Daniela Weber, M.D., Daigo Hashimoto, M.D., Ph.D., Ann E. Slingerland, B.S., John B. Slingerland, B.S., Molly Maloy, M.S., Annelie G. Clurman, B.A., Christoph K. Stein-Thoeringer, M.D., Kate A. Markey, M.B., B.S., Ph.D., Melissa D. Docampo, B.S., Marina Burgos da Silva, Ph.D., Niloufer Khan, M.D., André Gessner, M.D., Ph.D., Julia A. Messina, M.D., Kristi Romero, B.S., Meagan V. Lew, B.S., Amy Bush, B.A., Lauren Bohannon, B.S., Daniel G. Brereton, B.A., Emily Fontana, B.A., Luigi A. Amoretti, B.S., Roberta J. Wright, M.S., M.B.S., Gabriel K. Armijo, B.S., Yusuke Shono, M.D., Ph.D., Míriam Sanchez-Escamilla, M.D., Nerea Castillo Flores, M.D., Ph.D., Ana Alarcon Tomas, M.D., Richard J. Lin, M.D., Ph.D., Lucrecia Yáñez San Segundo, M.D., Ph.D., Gunjan L. Shah, M.D., Christina Cho, M.D., Michael Scordo, M.D., Ioannis Politikos, M.D., Kasumi Hayasaka, Yuta Hasegawa, M.D., Boglarka Gyurkocza, M.D., Doris M. Ponce, M.D., Juliet N. Barker, M.B., B.S., Miguel-Angel Perales, M.D., Sergio A. Giralt, M.D., Robert R. Jenq, M.D., Takanori Teshima, M.D., Ph.D., Nelson J. Chao, M.D., Ernst Holler, M.D., Joao B. Xavier, Ph.D., Eric G. Pamer, M.D., and Marcel R.M. van den Brink, M.D., Ph.D.
From the Adult Bone Marrow Transplantation Service (J.U.P., M.M., A.G.C., K.A.M., N.K., D.G.B., M.S.-E., N.C.F., A.A.T., R.J.L., L.Y.S.S., G.L.S., C.C., M.S., I.P., B.G., D.M.P., J.N.B., M.-A.P., S.A.G., M.R.M.B.) and the Infectious Disease Service (Y.T., E.F., L.A.A., R.J.W., E.G.P.), Department of Medicine, the Department of Epidemiology and Biostatistics (S.M.D.), the Department of Immunology, Sloan Kettering Institute (A.L.C.G., E.R.L., A.E.S., J.B.S., C.K.S.-T., M.D.D., M.B.S., G.K.A., Y.S., M.R.M.B.), and the Program for Computational and Systems Biology (J.B.X.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College (J.U.P., Y.T., K.A.M., M.D.D., R.J.L., G.L.S., C.C., M.S., I.P., B.G., D.M.P., J.N.B., M.-A.P., S.A.G., M.R.M.B.) — both in New York; Duchossois Family Institute of the University of Chicago, Chicago (E.R.L., E.G.P.); the Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center (A.D.S., M.V.L., A.B., L.B., N.J.C.), the Division of Infectious Diseases, Department of Medicine, Duke University (J.A.M.), and the Duke Office of Clinical Research, Duke University School of Medicine (K.R.) — all in Durham, NC; the Department of Hematology and Oncology, Internal Medicine III, University Medical Center (D.W., E.H.), the Collaborative Research Center Transregio 221 (D.W., A.G., E.H.), and Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg (A.G.) — all in Regensburg, Germany; the Department of Hematology, Hokkaido University Faculty of Medicine (D.H., Y.H., T.T.), and the Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital (K.H., T.T.) — both in Sapporo, Japan; Research Institute Marqués de Valdecilla–IDIVAL (M.S.-E.) and the Department of Hematology, Hospital Universitario Marqués de Valdecilla–IDIVAL, University of Cantabria (L.Y.S.S.), Santander, and Hospital Universitario Puerta de Hierro, Madrid (A.A.T.) — all in Spain; and the Departments of Genomic Medicine and Stem Cell Transplantation Cellular Therapy, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (R.R.J.). Address reprint requests to Dr. van den Brink at Memorial Sloan Kettering Cancer Center, 1275 York Ave., Box 111, New York, NY 10065, or at vandenbm@mskcc.org.

 

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