Metabolome and Microbiome Impact on Acute GVHD in Recipients of Hematopoietic Transplant

Condition(s) studied

Study summary

Recent published data suggest that specific alterations in intestinal metabolome signature of hematopoietic stem cell transplant (allo-SCT) recipients might influence incidence and severity of acute graft versus host disease (aGVHD). Nevertheless, this possible relationship has not been undoubtedly established, pathophysiologic mechanisms have not been elucidated and possible clinical implications have not been studied. We hypothesized that in the early phase of allo-SCT, specific alterations in faecal metabolome occurred related to loss of intestinal microbiota diversity and disbalance of specific bacterial taxa, and that both alterations determine reduced survival of patients through increased incidence and severity of aGVHD. To test this hypothesis, a prospective multi-center cohort of allo-SCT recipients will had faecal and plasmatic samples collected at predetermined time-points pre\&post-allo-SCT, and clinical relevant variables will be prospectively recorded throughout two years posttransplant follow-up. Metabolomic and microbiome analysis will be done to answer objectives of the study. To additionally explore if differential evolving characteristics in the intestinal metabolome and microbiome of donor/recipient sibling pairs influence the incidence and severity of aGVHD, probability of malignancy relapse and early and late mortality an additional cohort of family donors of enrolled patients will also have faecal and plasmatic samples collected and analysed.

Eligibility

Primary outcome measure(s)

• Metabolome — From pre-Conditioning (Day -15) to Day +100 post-transplant.
  Sequential pre-transplant/post-transplant modifications in faecal and plasmatic levels of: 1.a. Butyrate (targeted analysis), 1.b: Biliary acids (targeted analysis) and 1.c. Metabolomic signature (untargeted analysis).
• Incidence of Acute graft versus host disease — From the day of transplant (Day 0) to Day +100 posttransplant.
  Comparison of the incidence of any degree, degree-II and degree-III/IV of acute graft versus host disease between sub-groups of patients defined according to obtained metabolome results.
• Overall Survival — From the day of transplant (Day 0) to 2 years posttransplant.
  Comparison of overall survival between obtained groups according to metabolome results.
• Disease free survival — From the day of transplant (Day 0) to 2 years posttransplant.
  Comparison of overall survival between obtained groups according to metabolome results.

Trial sites (9)

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