Blood cancers

Microbiota health predicts success of allogeneic haematopoietic-cell transplantation

Survival outcomes after allogeneic haematopoietic-cell transplantation are dependent on diversity of intestinal microbiota at the time of neutrophil engraftment, international research has shown.

The study, run across four sites in the US, Germany and Japan, used 16S ribosomal RNA gene sequencing to assess microbiota disruption in 8,767 faecal samples from 1,362 patients with haematological cancers.

It found a loss of diversity was observed in patients at all four centres during the course of the transplantation period, despite local variations in microbiota composition and clinical practice.

Notably, patients already had a lower diversity than healthy volunteers on arrival for transplantation.

Patients with higher median diversity had a lower risk of death after transplantation than patients with lower diversity in univariate and multivariate analyses.

For example the death rates in the New York cohort were 29.4% in the higher-diversity group compared to 38.9% in the lower diversity group (HR = 0.75).

Samples with lower-diversity compositions were characterised by an abundance of enterococcus, klebsiella, escherichia, staphylococcus and streptococcus species, the study authors said.

“Enterococcus domination, a lower-diversity state that was previously shown to confer an increased risk of vancomycin-resistant enterococcal bacteremia as well as a higher risk of GVHD, occurred at all four centers.”

“Profound microbiota injuries — namely, loss of diversity and domination by single taxa — are common events that occur with strikingly convergent kinetics worldwide. These microbiota disruptions are of interest because lower diversity at the time of neutrophil engraftment predicts poor overall survival, particularly among recipients of T-cell replete grafts,” they wrote.

“Our results extend beyond microbial diversity to provide multicenter evidence that microbiota compositions — specifically the relative abundances of bacterial taxa — may offer relevant information about outcomes of allogeneic hematopoietic-cell transplantation.”

The study authors, published in NEJM, said strategies to remediate or prevent microbiota injury – including faecal microbiota replacement – either before transplantation or during the periengraftment period should be evaluated.

Haematologist Professor Jeff Szer, President of the Worldwide Network for Blood and Marrow Transplantation, told the limbic the role of microbiota was on the agenda at recent transplant and cellular therapy meetings in Orlando.

Research presented there included evidence that the oral microbiota is also disrupted during allogeneic HSCT.

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