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

N/AActive Not RecruitingNCT05186857

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla88 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Graft-versus-host Disease

Eligibility

Sex: ALLMin age: 1 YearMax age: 100 YearsHealthy volunteers:

Medical Language ↔ Plain English

Patients Patients receiving an allotransplant at participating hospitals during the study period before initiating conditioning period. Inclusion Criteria: * 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). Exclusion Criteria: * Unrelated donors * Transplants from umbilical cord blood source.

Locations (9)

Hospital Marqués de Valdecillas, Santander

Santander, Cantabria, Spain

Hospital Universitario Reina Sofía

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

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: From the day of transplant (Day 0) to Day +100 posttransplant.

Overall Survival

Comparison of overall survival between obtained groups according to metabolome results.

Time frame: 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.

Time frame: From the day of transplant (Day 0) to 2 years posttransplant.

Secondary Outcomes

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-

Time frame: At Day -15 and Day +30 post-transplant.

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-

Time frame: 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-

Time frame: 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-

Time frame: 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.

Time frame: 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.

Time frame: From the day of transplant (Day 0) to Days +30, +100, +365 and two years posttransplant.