SALT LAKE CITY — Diversity of gut microbiota at the time of neutrophil engraftment in allogeneic hematopoietic stem cell transplantation appeared associated with OS, according to results of an international multicenter cohort study presented at BMT Tandem Meetings.
“Our group and others have reported associations between microbiota composition and OS, as well as relapse, graft-versus-host disease, infections and toxicities,” Jonathan U. Peled, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center, said during his presentation. “One of the striking findings early on was this association between diversity in the gut and OS. ... A question I ask ... is, are the patterns of microbiota injury described in single-center studies and their associations with survival consistent across geography?”
Peled and colleagues compared microbiota diversity among patients who underwent allogeneic HSCT at Memorial Sloan Kettering, Duke University Medical Center and University of Regensburg in Germany.
Researchers sequenced and analyzed 5,823 samples from 1,118 patients.
The samples revealed no transplant center-specific effect. In addition, Enterococcus domination — a low-diversity state associated with Enterococcal bacteremia — occurred in all centers.
“The early samples tend to be more diverse. Many of the later clusters tend to be low-diversity states or injured microbiota compositions,” Peled said. “A typical transplantation patient may start out in this early diverse, healthy cluster but, as microbiota injury occurs, a patient may move into a various low-diversity injured state.”
Researchers used a multivariate linear regression model of diversity dynamics in a separate cohort at Memorial Sloan Kettering (n = 21) to determine relative contributions of antibiotics, nutrition and recovery from microbiota injury after discharge.
Results showed exposure to piperacillin-tazobactam (P < .01) and calorie intake (P < .05) served as predictors. Samples collected on the days of piperacillin-tazobactam administration contained lower diversity those collected on days without piperacillin-tazobactam (Simpson reciprocal, 4.15 ± 0.35 vs. 7.75 ± 0.21; P = 1.6-12).
Researchers also observed a correlation between calorie intake and diversity in the absence of piperacillin-tazobactam (r = 0.22; P = 2.95 x 10-5).
In the separate Memorial Sloan Kettering cohort, analysis of 37 samples indicated recovery from microbiota injury after allogeneic-HSCT. Samples showed gradual recovery of diversity at a rate in Simpson reciprocal of 2.17 per 100 days (P = .004).
Researchers confirmed an association between low diversity at the time of neutrophil engraftment and poor OS among a cohort from Memorial Sloan Kettering (n = 651; P = .006 for below- vs. above-median Simpson reciprocal) and a cohort from Regensburg (n = 59; P = .015).
“Microbiota injury occurs across geography. The association of diversity with OS is reproducible over time and geography,” Peled said. “Recovery from microbiota injury occurs gradually; with diversity increasing but often to a configuration distinct from the pretransplant state.” – by Melinda Stevens
Peled JU, et al. Abstract 3. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.
Disclosures: HemOnc Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.