Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study
Niloufer Khan, Sarah Lindner, Antonio L C Gomes, Sean M Devlin, Gunjan L Shah, Anthony D Sung, Craig S Sauter, Heather J Landau, Parastoo B Dahi, Miguel-Angel Perales, David J Chung, Alexander M Lesokhin, Anqi Dai, Annelie Clurman, John B Slingerland, Ann E Slingerland, Daniel G Brereton, Paul A Giardina, Molly Maloy, Gabriel K Armijo, Carlos Rondon-Clavo, Emily Fontana, Lauren Bohannon, Sendhilnathan Ramalingam, Amy T Bush, Meagan V Lew, Julia A Messina, Eric Littmann, Ying Taur, Robert R Jenq, Nelson J Chao, Sergio Giralt, Kate A Markey, Eric G Pamer, Marcel R M van den Brink, Jonathan U Peled, Niloufer Khan, Sarah Lindner, Antonio L C Gomes, Sean M Devlin, Gunjan L Shah, Anthony D Sung, Craig S Sauter, Heather J Landau, Parastoo B Dahi, Miguel-Angel Perales, David J Chung, Alexander M Lesokhin, Anqi Dai, Annelie Clurman, John B Slingerland, Ann E Slingerland, Daniel G Brereton, Paul A Giardina, Molly Maloy, Gabriel K Armijo, Carlos Rondon-Clavo, Emily Fontana, Lauren Bohannon, Sendhilnathan Ramalingam, Amy T Bush, Meagan V Lew, Julia A Messina, Eric Littmann, Ying Taur, Robert R Jenq, Nelson J Chao, Sergio Giralt, Kate A Markey, Eric G Pamer, Marcel R M van den Brink, Jonathan U Peled
Abstract
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.
Conflict of interest statement
Conflict-of-interest disclosure: N.K. received research funding from Gilead Sciences and an honorarium from Back Bay Life Sciences. S.L. received travel support from Celgene, Sanofi, and Neovii. A.L.C.G. received support from Seres Therapeutics. G.L.S. received research funding from Janssen and Amgen. A.D.S. received support from Seres Therapeutics. C.S.S. served as a consultant on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite (a Gilead Company), Celgene, Gamida Cell, and GlaxoSmithKline and received research funding for clinical trials from Juno Therapeutics, Celgene, Precision Biosciences, and Sanofi-Genzyme. H.J.L. served on advisory boards for Takeda, Janssen, and Celgene, served as a consultant for Caelum Biosciences and Karyopharm, and received research support from Takeda. M.-A.P. received honoraria from AbbVie, Bellicum, Celgene, Bristol Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda, served on data safety monitoring boards for Cidara Therapeutics, Servier, and Medigene and scientific advisory boards for MolMed and NexImmune, has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec, has served as a volunteer for and as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be The Match (National Marrow Donor Program), and on the Center for International Blood and Marrow Transplant Research Cellular Immunotherapy Data Resource Committee. D.J.C. received research funding from Genentech. A.E.S. received support from Seres Therapeutics. R.R.J. has consulted for Karius, Merck, Microbiome DX, and Prolacta, has served on the scientific advisory boards of Kaleido, Maat Pharma, and Seres, and has received patent royalties licensed to Seres. S.G. received research funding from Amgen, Actinuum, Celgene, Johnson & Johnson, Miltenyi, Takeda, and Omeros, and has served on advisory boards for Amgen, Actinuum, Celgene, Johnson & Johnson, Janssen, Jazz Pharmaceutical, Takeda, Novartis, Kite, and Spectrum Pharma. K.A.M received travel support and honoraria or consulting fees from Karius. E.G.P. has received speaker honoraria from Bristol Myers Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis, and Ferring Pharmaceuticals and is an inventor on patent application #WPO2015179437A1 (entitled “Methods and compositions for reducing Clostridium difficile infection”) and #WO2017091753A1 (entitled “Methods and compositions for reducing vancomycin-resistant enterococci infection or colonization”) and holds patents that receive royalties from Seres Therapeutics. M.R.M.v.d.B. has received research support and stock options from Seres; has received stock options from Notch Therapeutics; has received royalties from Wolters Kluwer; consulted and received honorarium from, or participated in, advisory boards for Seres Therapeutics, Jazz Pharmaceuticals, Rheos, Therakos, WindMIL Therapeutics, Amgen, Merck & Co, Inc, Magenta Therapeutics, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Forty Seven Inc, Priothera, Ceramedix, DKMS (Deutsche KnochenMarkSpenderdatei), Pharmacyclics (spouse), Kite Pharmaceuticals (spouse); has IP Licensing with Seres Therapeutics and Juno Therapeutics; and holds a fiduciary role on the Foundation Board of DKMS (a nonprofit organization). J.U.P. has received research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics and consulting fees from DaVolterra. The remaining authors declare no competing financial interests.
© 2021 by The American Society of Hematology.
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Source: PubMed