EBMT 2018 | Can microbiome markers predict acute GvHD after allo-HSCT?

At the 44^th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) held in Lisbon, Portugal, from March 18-21 2018 an oral abstract session was held and an oral abstract was presented by Raffaella Greco from IRCCS San Raffaele Scientific Institute, Hematology and Bone Marrow Transplantation Unit, Milan, Italy, entitled “Microbiome markers are early predictors of acute GvHD in allogeneic hematopoietic stem cell transplant recipients”. This article is based on data from the presentation and may supersede that presented in the published abstract.

Doctor Greco began her talk by setting the scene for the work. Recent studies have shown that longitudinal analysis of microbiome profile allows early identification of patients at risk for major transplant-related complications such as acute graft-versus-host disease (aGvHD). Thus, the study group retrospectively analyzed the role of intestinal microbiota in the setting of aGvHD in 100 consecutive adult patients, who previously underwent allogeneic HSCT between October 2014 and March 2016.

Patients and methods:

• Stem cell donors were:
  • family haploidentical (n=45)
  • HLA identical sibling (n=15)
  • unrelated volunteer (n=35)
  • cord blood (n=5)
• Fecal specimens were collected before conditioning (T0), during aplasia (T10) and after engraftment (T30)
• 454 GS Junior System and QIIME software were used to analyse the fecal microbiome
• Acute GvHD was defined and scored according to the Glucksberg criteria

Key data:

• Development of early aGvHD (within 30 days) = 25.27%
• Development of late aGvHD (within 100 days) = 50.55%
• Overall incidence of aGvHD of grade I-II = 30.76%
• Overall incidence of aGvHD of grade III-IV = 19.78%
• Skin only involvement = 34.56%
• Gut only involvement = 8.69%
• Skin and gut involvement = 8.69%
• Liver and gut involvement = 1.04%
• Skin, liver and gut involvement = 7.29%
• Development of aGvHD led to significant modifications in intestinal microbiota composition:
  • Firmicutes
  • Lachnospiraceae was associated to a decreased risk of developing aGvHD, P = 0.04 and RR = 4.35
  • Enterococcaceae and Staphylococcaceae was associated to increased incidence of aGvHD
  • Microbiome markers were more informative at 10 days after transplant (T1) with a low α-diversity (Shannon index) being significantly correlated to increased risk of early acute GvHD, P = 0.01, grade 3-4 acute GvHD, P = 0.008
  • Dominance of Staphylococcaceae predicted grade 3-4 aGvHD, P = 0.03
    • Liver GvHD, P = 0.004
    • Gut GvHD, P = 0.03
    • Steroid-refractory GvHD, P = 0.05
  • Enterococcaceae were significantly higher in patients who developed early acute GvHD, P = 0.01, especially in those with gut involvement, P = 0.01
  • Dominance of Enterococcaceae was correlated with late aGvHD, P = 0.0006

These findings confirmed that the microbiome profile may influence aGvHD. Doctor Greco further added that “a longitudinal study of microbioma profile allows early identification of patients at risk for aGvHD, offering a new tool for individualized approaches for preventing and treating acute GvHD.”