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| Name | Class |
|---|---|
| Instituto de Salud Carlos III | OTHER_GOV |
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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.
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| Measure | Description | Time Frame |
|---|---|---|
| Metabolome | 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). | From pre-Conditioning (Day -15) to Day +100 post-transplant. |
| Incidence of Acute graft versus host disease | 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. | From the day of transplant (Day 0) to Day +100 posttransplant. |
| Overall Survival | Comparison of overall survival between obtained groups according to metabolome results. | From the day of transplant (Day 0) to 2 years posttransplant. |
| Disease free survival | Comparison of overall survival between obtained groups according to metabolome results. | From the day of transplant (Day 0) to 2 years posttransplant. |
| Measure | Description | Time Frame |
|---|---|---|
| Microbiome (alpha diversity of the intestinal microbiota) | 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- | At Day -15 and Day +30 post-transplant. |
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Patients Patients receiving an allotransplant at participating hospitals during the study period before initiating conditioning period.
Inclusion Criteria:
Exclusion Criteria
- Allotransplant recipients in stages after the initial pre-conditioning.
Donors
Family donors from patients included in the study:
Inclusion criteria:
Exclusion Criteria:
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Patients receiving an allotransplant and family donors of the included patients.
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| Name | Affiliation | Role |
|---|---|---|
| Ildefonso Espigado, PhD | Seville University, Dep. of Medicine. Virgen del Rocío/Virgen Macarena Hospitals, Instituto de Investigación Biomédica de Sevilla / CSIC, Seville, Spain | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Marqués de Valdecillas, Santander | Santander | Cantabria | Spain | |||
| Hospital Universitario Reina Sofía |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| Microbiome (beta diversity of the intestinal microbiota) |
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- |
| At Day -15 and Day +30 post-transplant. |
| Microbiome (alpha diversity of the plasmatic microbiota) | 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- | At Day -15 and Day +30 post-transplant. |
| Microbiome (beta diversity of the plasmatic microbiota) | 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- | At Day -15 and Day +30 post-transplant. |
| Relapse | Comparison of patients´s incidence of relapse of the malignant disease between the groups obtained according to microbiome-metabolome results. | From the day of transplant (Day 0) to +30, +100, +365 and two years posttransplant. |
| Mortality | Comparison of patients mortality between the groups obtained according to microbiome-metabolome results. | From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant. |
| Córdoba |
| Córdoba |
| Spain |
| Hospital Virgen de las Nieves de Granada | Granada | Granada | Spain |
| Hospital del Niño Jesús, Madrid | Madrid | Madrid | Spain |
| Hospital La Paz, Madrid | Madrid | Madrid | Spain |
| Hospital Regional Universitario de Málaga | Málaga | Málaga | Spain |
| Hospital Clínico de Salamanca | Salamanca | Salamanca | Spain |
| Hospital Universitario Virgen del Rocío, Sevilla | Seville | Seville | Spain |
| Hospital Clínico de Valencia | Valencia | Valencia | Spain |