Enteric Microbiome Markers as Early Predictors of Clinical Outcome in Allogeneic Hematopoietic Stem Cell Transplant: Results of a Prospective Study in Adult Patients

BACKGROUND: Infections and graft-vs-host disease (GvHD) still represent major, not easily predictable complications in allogeneic hematopoietic stem cell transplant (allo-HSCT). Both conditions have been correlated to altered enteric microbiome profiles during the peritransplant period. The main objective of this study was to identify possible early microbiome-based markers useful in pretransplant risk stratification. METHODS: Stool samples were collected from 96 consecutive patients at the beginning of the pretransplant conditioning regimen (T(0)) and at 10 (T(1)) and 30 (T(2)) days following transplant. When significant in univariate analysis, the identified microbiome markers were used in multivariate regression analyses, together with other significant clinical variables for allo-HSCT-related risk stratification. Four main outcomes were addressed: (1) septic complications, (2) GvHD, (3) relapse of the underlying disease, and (4) mortality. RESULTS: The presence of >5% proinflammatory Enterobacteriaceae at T(0) was the only significant marker for the risk of microbiologically confirmed sepsis. Moreover, ≤10% Lachnospiraceae at T(0) was the only significant factor for increased risk of overall mortality, including death from both infectious and noninfectious causes. Finally, a low bacterial alpha-diversity (Shannon index ≤ 1.3) at T(1) was the only variable significantly correlating with an increased risk of GvHD within 30 days. CONCLUSIONS: Microbiome markers can be useful in the very early identification of patients at risk for major transplant-related complications, offering new tools for individualized preemptive or therapeutic strategies to improve allo-HSCT outcomes.