Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study

被引：51

作者：

Khan, Niloufer ^{[1
]}

Lindner, Sarah ^{[2
]}

Gomes, Antonio L. C. ^{[2
]}

Devlin, Sean M. ^{[3
]}

Shah, Gunjan L. ^{[1
,4
]}

Sung, Anthony D. ^{[5
]}

Sauter, Craig S. ^{[1
,4
]}

Landau, Heather J. ^{[1
,4
]}

Dahi, Parastoo B. ^{[1
,4
]}

Perales, Miguel-Angel ^{[1
,4
]}

Chung, David J. ^{[1
,4
]}

Lesokhin, Alexander M. ^{[4
,6
]}

Dai, Anqi ^{[2
]}

Clurman, Annelie ^{[1
]}

Slingerland, John B. ^{[1
]}

Slingerland, Ann E. ^{[1
]}

Brereton, Daniel G. ^{[1
]}

Giardina, Paul A. ^{[1
]}

Maloy, Molly ^{[1
]}

Armijo, Gabriel K. ^{[2
]}

Rondon-Clavo, Carlos ^{[1
]}

Fontana, Emily ^{[2
]}

Bohannon, Lauren ^{[5
]}

Ramalingam, Sendhilnathan ^{[5
]}

Bush, Amy T. ^{[5
]}

Lew, Meagan, V ^{[5
]}

Messina, Julia A. ^{[7
]}

Littmann, Eric ^{[8
]}

Taur, Ying ^{[4
,9
]}

Jenq, Robert R. ^{[10
]}

Chao, Nelson J. ^{[5
]}

Giralt, Sergio ^{[1
,4
]}

Markey, Kate A. ^{[1
,4
]}

Pamer, Eric G. ^{[8
]}

van den Brink, Marcel R. M. ^{[1
,2
,4
]}

Peled, Jonathan U. ^{[1
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, Dept Med, 1275 York Ave,ZRC 1419, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Immunol, Sloan Kettering Inst, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[4] Weill Cornell Med Coll, New York, NY USA

[5] Duke Univ, Dept Med, Div Hematol Malignancies & Cellular Therapy, Sch Med, Durham, NC USA

[6] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, New York, NY 10065 USA

[7] Duke Univ, Dept Med, Div Infect Dis, Sch Med, Durham, NC USA

[8] Univ Chicago, Duchossois Family Inst, Chicago, IL 60637 USA

[9] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, New York, NY 10021 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

来源：

BLOOD | 2021年 / 137卷 / 11期

基金：

美国国家卫生研究院;

关键词：

STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; TREATMENT-RELATED MORTALITY; GUT MICROBIOTA; INTESTINAL MICROBIOTA; EFFICACY; MELPHALAN; LYMPHOMA; AUGMENTS; EXPOSURE;

D O I：

10.1182/blood.2020006923

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States. By using 16S ribosomal gene sequencing, we assessed fecal microbiota composition and diversity, as measured by the inverse Simpson index. At both centers, the diversity of early pretransplant fecal microbiota was lower in patients than in healthy controls and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to those with allo-HCT. Above-median fecal intestinal diversity in the periengraftment period was associated with decreased risk of death or progression (progression-free survival hazard ratio, 0.46; 95% confidence interval, 0.26-0.82; P=.008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and posttransplant outcomes should be undertaken.

引用

页码：1527 / 1537

页数：11

共 70 条

[1] Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation [J].

Arpaia, Nicholas ;

Campbell, Clarissa ;

Fan, Xiying ;

Dikiy, Stanislav ;

van der Veeken, Joris ;

deRoos, Paul ;

Liu, Hui ;

Cross, Justin R. ;

Pfeffer, Klaus ;

Coffer, Paul J. ;

Rudensky, Alexander Y. .

NATURE, 2013, 504 (7480) :451-+

[2] Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota [J].

Arthur, Janelle C. ;

Perez-Chanona, Ernesto ;

Muehlbauer, Marcus ;

Tomkovich, Sarah ;

Uronis, Joshua M. ;

Fan, Ting-Jia ;

Campbell, Barry J. ;

Abujamel, Turki ;

Dogan, Belgin ;

Rogers, Arlin B. ;

Rhodes, Jonathan M. ;

Stintzi, Alain ;

Simpson, Kenneth W. ;

Hansen, Jonathan J. ;

Keku, Temitope O. ;

Fodor, Anthony A. ;

Jobin, Christian .

SCIENCE, 2012, 338 (6103) :120-123

[3] Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma [J].

Attal, Michel ;

Lauwers-Cances, Valerie ;

Hulin, Cyrille ;

Leleu, Xavier ;

Caillot, Denis ;

Escoffre, Martine ;

Arnulf, Bertrand ;

Macro, Margaret ;

Belhadj, Karim ;

Garderet, Laurent ;

Roussel, Murielle ;

Payen, Catherine ;

Mathiot, Claire ;

Fermand, Jean P. ;

Meuleman, Nathalie ;

Rollet, Sandrine ;

Maglio, Michelle E. ;

Zeytoonjian, Andrea A. ;

Weller, Edie A. ;

Munshi, Nikhil ;

Anderson, Kenneth C. ;

Richardson, Paul G. ;

Facon, Thierry ;

Avet-Loiseau, Herve ;

Harousseau, Jean-Luc ;

Moreau, Philippe .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (14) :1311-1320

[4] Fifty Years of Melphalan Use in Hematopoietic Stem Cell Transplantation [J].

Bayraktar, Ulas D. ;

Bashir, Qaiser ;

Qazilbash, Muzaffar ;

Champlin, Richard E. ;

Ciurea, Stefan O. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2013, 19 (03) :344-356

[5] Transplantation related toxicity and mortality in older autologous hematopoietic cell transplantation recipients [J].

Belete, Hewan ;

Burns, Linda J. ;

Shanley, Ryan ;

Nayar, Manju ;

McClune, Brian ;

Lazaryan, Aleksandr ;

Bachanova, Veronika ;

Bejanyan, Nelli ;

Ustun, Celalettin ;

Brunstein, Claudio ;

Weisdorf, Daniel J. ;

Arora, Mukta .

AMERICAN JOURNAL OF HEMATOLOGY, 2017, 92 (09) :E529-E533

[6] Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression [J].

Calcinotto, Arianna ;

Brevi, Arianna ;

Chesi, Marta ;

Ferrarese, Roberto ;

Perez, Laura Garcia ;

Grioni, Matteo ;

Kumar, Shaji ;

Garbitt, Victoria M. ;

Sharik, Meaghen E. ;

Henderson, Kimberly J. ;

Tonon, Giovanni ;

Tomura, Michio ;

Miwa, Yoshihiro ;

Esplugues, Enric ;

Flavell, Richard A. ;

Huber, Samuel ;

Canducci, Filippo ;

Rajkumar, Vincent S. ;

Bergsagel, P. Leif ;

Bellone, Matteo .

NATURE COMMUNICATIONS, 2018, 9

[7] Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab [J].

Chaput, N. ;

Lepage, P. ;

Coutzac, C. ;

Soularue, E. ;

Le Roux, K. ;

Monot, C. ;

Boselli, L. ;

Routier, E. ;

Cassard, L. ;

Collins, M. ;

Vaysse, T. ;

Marthey, L. ;

Eggermont, A. ;

Asvatourian, V. ;

Lanoy, E. ;

Mateus, C. ;

Robert, C. ;

Carbonnel, F. .

ANNALS OF ONCOLOGY, 2017, 28 (06) :1368-1379

[8] High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma [J].

Child, JA ;

Morgan, GJ ;

Davies, FE ;

Owen, RG ;

Bell, SE ;

Hawkins, K ;

Brown, J ;

Drayson, MT ;

Selby, PJ .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (19) :1875-1883

[9] T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of Immunotherapy [J].

Chung, David J. ;

Pronschinske, Katherine B. ;

Shyer, Justin A. ;

Sharma, Sneh ;

Leung, Samantha ;

Curran, Shane A. ;

Lesokhin, Alexander M. ;

Devlin, Sean M. ;

Giralt, Sergio A. ;

Young, James W. .

CANCER IMMUNOLOGY RESEARCH, 2016, 4 (01) :61-71

[10] Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-01 [J].

d'Amore, Francesco ;

Relander, Thomas ;

Lauritzsen, Grete F. ;

Jantunen, Esa ;

Hagberg, Hans ;

Anderson, Harald ;

Holte, Harald ;

Osterborg, Anders ;

Merup, Mats ;

Brown, Peter ;

Kuittinen, Outi ;

Erlanson, Martin ;

Ostenstad, Bjorn ;

Fagerli, Unn-Merete ;

Gadeberg, Ole V. ;

Sundstrom, Christer ;

Delabie, Jan ;

Ralfkiaer, Elisabeth ;

Vornanen, Martine ;

Toldbod, Helle E. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (25) :3093-3099

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