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Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.

ABSTRACT: Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2067 stool samples and flow cytometry data from 2370 peripheral blood samples drawn from 894 patients who underwent allogeneic HCT, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts. We observed that fecal microbial diversity was an independent predictor of CD4 T-cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early posttransplant period was associated with worse CD4 T-cell recovery. Our observations suggest that the intestinal bacteria, or the factors they produce, can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation.

SUBMITTER: Miltiadous O

PROVIDER: S-EPMC9074404 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.

Miltiadous Oriana O Waters Nicholas R NR Andrlová Hana H Dai Anqi A Nguyen Chi L CL Burgos da Silva Marina M Lindner Sarah S Slingerland John J Giardina Paul P Clurman Annelie A Armijo Gabriel K GK Gomes Antonio L C ALC Lakkaraja Madhavi M Maslak Peter P Scordo Michael M Shouval Roni R Staffas Anna A O'Reilly Richard R Taur Ying Y Prockop Susan S Boelens Jaap Jan JJ Giralt Sergio S Perales Miguel-Angel MA Devlin Sean M SM Peled Jonathan U JU Markey Kate A KA van den Brink Marcel R M MRM

Blood 20220501 18

Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2067 stool samples and flow cytometry data from 2370 peripheral blood samples drawn from 894 patients who underwent allogeneic HCT, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts ...[more]

PMID: 35061893

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Project description:Importance:Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective:To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants:In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures:Allogeneic hematopoietic cell transplant. Main Outcomes and Measures:Survival trends, disease relapse, and toxicity. Results:A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance:Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

Dataset Information

Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.

Publications

Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant.

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