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EBMT 2020 Annual Meeting - Educational forum on microbiota and allogeneic HSCT

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Saturday 29 August, 15:00-16:00H, Auditorium 1

Understanding of the impact of the microbiome on HSCT and haematology more generally continues to evolve. In the first talk in this three-part session, Dr Daniela Weber (University Hospital Regensburg, Germany) addresses how the microbiome affects haematopoietic stem cell transplantation (HSCT) alloreactive phenomena and outcomes.

“Although allogeneic stem cell transplantation (ASCT) is a potentially curative treatment option for various haematological diseases, acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality, and its management is clinically very important,” says Dr Weber. She will discuss previous serial analyses of faecal specimens from ASCT recipients, which showed a loss of intestinal microbiome diversity and a shift to an enteropathogenic flora.

“Intensive microbiota disruptions with a loss of protective commensal bacteria like Clostridiales and their protective metabolites such as indoles and short chain fatty acids (SCFAs) –particularly around the time of engraftment – seem to be associated with a significantly worse clinical outcome mainly due to acute GI GvHD,” she explains. “Both indoles and SCFAs stabilise epithelial integrity and modulate immunoregulatory cells towards a tolerogeneic phenotype. These single centre observations could soon be confirmed for the first time by a multicentre observational study including four transplant centers on three continents.”

She will also explain how multiple risk factors contribute to a significant intestinal dysbiosis including conditioning toxicity, alterations in nutrition, damage of epithelial cells by GvHD itself and, of course, the use of broad-spectrum antibiotics. “Here, not only the type of antibiotic therapy but also the beginning of systemic antibiotics significantly influences acute GI GvHD-associated transplant-related mortality,” she explains.

Dr Weber will discuss that these clinical results suggest that correction of intestinal dysbiosis, for example by faecal microbiota transplantation, may be a promising strategy for treatment and prevention of acute GI GvHD. She concludes: “Furthermore, intervention in the gut microbiota with a nutritional approach including prebiotics or postbiotics, and antibiotic selection may also be promising options for prophylaxis or treatment of acute GI GvHD.”

In the second presentation, Professor Riccardo Masetti (Pediatric Oncology and Hematology, University of Bologna, Italy) will discuss that there is now general agreement in the transplant community that gut microbiota (GM) composition can affect clinical outcomes after allogeneic HSCT, and will discuss the situation in paediatrics.

“Strong evidence generated in adult HSCT setting has clearly shown how profound microbiota changes, namely the loss of diversity and domination by a single species, negatively affect outcomes,” explains Professor Masetti. “As there are few data available on cohorts of transplanted children, we aimed to study if these associations are generalisable in an exclusive paediatric HSCT setting.”

He will detail how his team prospectively studied GM dynamics in relation to the development of acute GvHD. “In our model, the composition and diversity of the GM, as it is before HSCT takes place, might lack features of a healthy-like community, or include risk factors for localised mucosal damage, thus losing its resilience and evolving into a so-called ‘pathobiome’. This scenario could be important in strategies to manipulate the pre-HSCT GM.”

He will also show, using a prospective evaluation of the whole gut resistome, how the individual GM of HSCT children can act as a dynamic reservoir of antibiotic-resistant bacteria, with the potential to develop an antimicrobial resistance gene pattern following HSCT. Finally, looking for the best approach to modulate towards a more diverse and “protective” GM configuration, Professor Masetti will show how enteral nutrition during HSCT promotes the achievement of GM homeostasis and a prompt GM structural and functional recovery already starting from 30 days post-HSCT.   

The final talk in this session ‘preventive and therapeutic interventions in the microbiota’ will be given by Associate Professor Florent Mallard, based at the Haematology and Cell Therapy Department at Saint Antoine Hospital, Sorbonne University, Paris, France. He explains that “loss of bacterial diversity at engraftment has been correlated with a worse outcome after allogeneic hematopoietic cell transplantation (alloHCT). In particular, enterobacterieceae and enterococcus are associated with a decreased overall survival (OS) and a GvHD-related mortality.”

In contrast, Clostridiales are associated with an improved outcome: reduced mortality for Lachnospiraceae and Ruminococcaeae, less GvHD for Blautia and even decreased relapse rate for Eubacterium limosum. “Therefore, several strategies of microbiota manipulation are under development to prevent or to treat these complications. In particular, several studies evaluate the impact timing or initiation or discontinuation of prophylactic and empiric fever antibiotic treatment on microbiota composition and patients’ outcomes. Similarly use of prebiotics is an emerging strategy to modulate gut microbiota after alloHCT,” says Associate Professor Mallard.

In the last part of his presentation, he will address how use of probiotics and especially faecal microbiota transplantation has shown some very promising results for the treatment of GvHD and also offer some perspective on using these as a strategy to restore gut microbiota composition and prevent complications after alloHCT.