Patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who have greater intestinal microbiota diversity may have a lower risk for mortality, according to research published in The New England Journal of Medicine.
Allo-HCT, which may be curative in a number of hematologic malignancies, is linked to severe complications that pose significant risk for mortality. Some single-center studies have suggested that intestinal microbiota diversity is linked to outcomes after allo-HCT, though this had not previously been evaluated in a large, multicenter trial. Given that antibiotic use and nutrition play a significant role in determining microbiota diversity, multicenter analysis is essential for determining a link between diversity and patient outcomes.
For this study, researchers evaluated data from 4 institutions to determine any patterns of microbiota disruption after allo-HCT, as well as whether disruption is linked to outcomes, among patients undergoing transplant for a hematologic malignancy.
Overall, 1362 patients were included in the study; 61% of patients were male and 57% underwent an ablative conditioning regimen. The most common disease was acute myeloid leukemia (36%), followed by myelodysplastic syndrome or myeloproliferative neoplasm (19%) and non-Hodgkin lymphoma (17%).
The researchers profiled 8767 stool samples from the overall study group, which was split into 2 cohorts: Cohort 1 included 1076 patients treated at Memorial Sloan Kettering Cancer Center and cohort 2 included the 286 patients treated at the remaining 3 centers. In both cohorts, domination by a single taxa and general loss of diversity after transplant were noted patterns.
Patients in each cohort were grouped into higher diversity and lower diversity groups. In cohort 1, there were 104 deaths among the 354 patients in the higher diversity group compared with 136 deaths among the 350 patients in the lower diversity group (adjusted hazard ratio [HR], 0.71; 95% CI, 0.55-0.92). In cohort 2, there were 18 deaths among the 87 patients in the higher diversity group compared with 35 deaths among the 92 patients in the lower diversity group (adjusted HR, 0.49; 95% CI, 0.27-0.90).
Compared with a group of healthy volunteers, initial stool samples appeared to have lower microbiota diversity. Baseline samples suggested evidence of microbiota disruption prior to allo-HCT, and lower diversity prior to the procedure was linked to worse survival: In cohort 1, higher diversity prior to allo-HCT carried an adjusted HR for mortality of 0.41 (95% CI, 0.24-0.71).
“In patients undergoing [allo-HCT], these associations were observed consistently across graft sources, conditioning regimens, and around the world, despite local variations in microbiota composition and clinical practice,” the researchers noted.
1. Peled JU, Gomes ALC, Devlin SM, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation [published online February 27, 2020]. N Engl J Med. doi: 10.1056/NEJMoa1900623