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INTESTINAL MICROBIOTA CAN PREDICT AGVHD FOLLOWING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

S1623

Han, L.1, 2; Zhang, H.2; Chen, S.2; Zhao, K.2; Huang, F.2; Fan, Z.2; Jin, H.2; Jiang, Z.1; Liu, Q.-F.2

doi: 10.1097/01.HS9.0000564740.31251.8b
Simultaneous Sessions IV: Graft-versus-Host Disease
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1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou

2Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China, Guangzhou, China

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Background:

The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD), and loss of microbiota diversity is associated with aGVHD. However, it has been rarely reported whether the intestinal microbiota at neutrophil engraftment could predict the occurrence and grades of aGVHD.

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Aims:

We collected stool and blood samples from 141 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at pre-conditioning, day 0 and day 15 post-transplantation. The microbiota in stool were detected by 16S rRNA gene sequencing; the inflammatory factors in blood were detected by multiplex immunoassays and dynamic turbidimetric methods; and T lymphocyte subsets were tested by flow cytometry.

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Methods:

The microbiota diversity was lower in the aGVHD group compared with non-aGVHD group at day 0 and day 15 ± 1 (P = 0.018 and 0.009, respectively). Diversity was associated with conditioning (P = 0.017, day 0 and P = 0.045, day 15) and β-lactam antibiotics (P = 0.004, day 15). The Treg/Th17 ratio in blood was positively correlated with microbial diversity (r = 0.216, P = 0.010), while it was negatively correlated with the levels of TNF-α, IL-17A, IL-1β and LPS in plasma (r = −0.226, −0.225, −0.335, −0.291; P = 0.007, 0.010, < 0.001, < 0.001, respectively) at day 15 post-transplantation. In addition, the accumulated intestinal microbiota (AIM) score at day 15 could be a predictor for the development of aGVHD (II-IV aGVHD: AUC = 0.75, P < 0.001; III-IV aGVHD: AUC = 0.84, P < 0.001). The AIM score was also correlated with aGVHD grades (r = 0.481, P < 0.001).

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Results:

These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD.

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Summary/Conclusion:

These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.