Metabolome and Microbiome Impact on Acute GVHD in Recipients of Hematopoietic Transplant
- Conditions
- Graft-versus-host Disease
- Registration Number
- NCT05186857
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 88
- Patients of any age who will receive allogeneic hematopoietic transplantation of any modality with any diagnosis.
- Agreement of the patient to participate by signing the informed consent or his/her legal representatives/assent (if applicable).
Exclusion Criteria
- Allotransplant recipients in stages after the initial pre-conditioning.
Donors
Family donors from patients included in the study:
Inclusion criteria:
- Agreement of the donor to participate by signing the informed consent or his/her legal representatives/assent (if applicable).
- Donor relatives with any degree of identity in the Human Leukocyte Antigens (HLA).
- Unrelated donors
- Transplants from umbilical cord blood source.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.
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.
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).
Overall Survival From the day of transplant (Day 0) to 2 years posttransplant. Comparison of overall survival between obtained groups according to metabolome results.
- Secondary Outcome Measures
Name Time Method Microbiome (alpha diversity of the intestinal microbiota) At Day -15 and Day +30 post-transplant. Comparison of biological alpha diversity of the intestinal microbiota. Calculation of alpha diversity (Shannon's diversity index, observed OTUs, Faith's Phylogenetic Diversity and Evenness) index by QIIME-
Relapse From the day of transplant (Day 0) to +30, +100, +365 and two years posttransplant. Comparison of patients´s incidence of relapse of the malignant disease between the groups obtained according to microbiome-metabolome results.
Mortality From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant. Comparison of patients mortality between the groups obtained according to microbiome-metabolome results.
Microbiome (beta diversity of the intestinal microbiota) At Day -15 and Day +30 post-transplant. Comparison of biological beta diversity of the intestinal microbiota. Calculation of beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFrac distance and Unweighted UniFrac distance) index by QIIME-
Microbiome (beta diversity of the plasmatic microbiota) At Day -15 and Day +30 post-transplant. Comparison of biological beta diversity of the plasmatic microbiota. Calculation of beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFrac distance and Unweighted UniFrac distance) index by QIIME-
Microbiome (alpha diversity of the plasmatic microbiota) At Day -15 and Day +30 post-transplant. Comparison of biological alpha diversity of the plasmatic microbiota. Calculation of alpha diversity (Shannon's diversity index, observed OTUs, Faith's Phylogenetic Diversity and Evenness) index by QIIME-
Trial Locations
- Locations (9)
Hospital del Niño Jesús, Madrid
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Marqués de Valdecillas, Santander
🇪🇸Santander, Spain
Hospital Clínico de Salamanca
🇪🇸Salamanca, Spain
Hospital La Paz, Madrid
🇪🇸Madrid, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Virgen de las Nieves de Granada
🇪🇸Granada, Spain
Hospital Universitario Virgen del Rocío, Sevilla
🇪🇸Sevilla, Seville, Spain
Hospital Clínico de Valencia
🇪🇸Valencia, Spain