PracticeUpdate Conference Series ASH 2018

Microbiome Injury Prior to Hematopoietic Stem Cell Transplantation Predicts Survival Strategies that treat microbiome injury pre-transplant may lead to better patient outcomes.

P re-hematopoietic stem cell transplantation (HSCT) microbiota injury is prevalent across institutions and predicts poor overall patient survival, according to research presented at ASH 2018. “The intestinal microbiome harbors the highest density of bacteria in any location on the planet,” said Jonathan Peled, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, during his presentation. “We have as many bacteria cells in and on our body as we have human cells. We are actual ecosystems walking around.” “Our immune systems are really maintaining homeostasis – or an equilibrium balance – with the bacteria that we co-evolved with,” he added. “You can interpret many immune reactions as perturbations from that equilibrium.” Dr. Peled pointed out that after allogeneic HSCT, there are four causes of death: relapse, infection, graft versus host disease, and organ toxicity. “Each of these outcomes has been associated with the composition of the gut microbiota,” he said. However, these observations have been based on single-center studies that characterized the micro- biota in the first weeks after transplantation. In this study, Dr. Peled and his colleagues hypothesized that microbiota configuration pre-HSCT could also be a predictor of post-transplantation outcomes.

Dr. Peled and his colleagues collected stool sam- ples from 991 adult allogeneic HSCT patients at four international transplant centers (two in the United States, one in Europe, and one in Japan). These patients varied with respect to underlying diagnosis, donor graft sources, conditioning inten- sity, and GVHD prophylaxis. Patients from all four centers had reduced micro- biota diversity pre-HSCT with inverse Simpson index (α-diversity) measurements that ranged from 1.7- to 2.5-fold lower than those values of healthy volunteers (P < .005). And the microbial communi- ties in the majority of patients’ guts went on to be dominated by a single bacterial species. When looking at these pre-HSCT communities across institutions, they found in the largest cohort of 753 patients (one of the transplantation centers in the United States) that pre-HSCT microbiota diversity is associated with patient survival. Those patients in the lowest quartile of pre-HSCT micro- biota diversity had lower overall survival than patients in the highest quartile (P < .009). The study findings demonstrated that HSCT patients across the four institutions in three continents had microbiota configurations that were similar to one another and different from healthy individuals, and

" … if we come up with a way to remediate microbiome injury, there might be time to implement it before the transplant. "

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PRACTICEUPDATE CONFERENCE SERIES • ASH 2018