International Study: Microbiota Injury Before HCT Is Prevalent and Predicts Poor Survival

An international group of researchers examined whether microbiota configuration prior to hematopoietic cell transplantation (HCT) could determine outcomes after transplant, including survival, relapse, infections, and graft-versus-host disease (GVHD). Their presentation at the ASH annual meeting, microbiota configuration had previously been studied only at single institutions and only in the weeks following HCT.

According to Jonathan U. Peled, MD, PhD, of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, and colleagues, patients at four institutions on three continents presented with microbiota configurations that were similar and distinct from those of healthy individuals.

“Severe microbiota injury is a common event whose development begins before allograft infusion, and pre-HCT microbiota injury predicts poor overall survival,” he added.

The researchers collected 1,922 stool samples about weekly from 991 adult patients receiving allogeneic HCT at two transplant centers in the United States, one in Europe, and one in Japan. The patients had varying underlying diagnoses, sources of donor grafts, conditioning intensities, and methods for GVHD prophylaxis. The samples all were sequenced and analyzed at the same laboratory.

According to the findings, patients from all four centers had reduced microbiota diversity before HCT, as compared to healthy volunteers sequenced either by the study researchers or available in a public dataset. Additionally, the differences in samples across geography were very small in magnitude. In the largest cohort, low diversity was associated with exposure to broad-spectrum antibiotics, conditioning intensity, and low calorie intake. Finally, also in the largest cohort, pre-HCT diversity was associated with survival.

The researchers concluded that, together, the results reveal a “window of opportunity,” and they encouraged healthcare teams to evaluate microbiota injury before HCT to determine comorbidities and select appropriate treatments (such as antibiotics, prophylaxis for GVHD, and conditioning regimens), adding that knowledge before HCT could inform strategies to remediate or prevent microbiota injury.