Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation
Conditions
Keywords
microbiota, microbiome, graft versus host disease, infection, antibiotics
Brief summary
There are data suggesting that the reduction of the diversity of intestinal microbiota caused by the used treatments in the setting of allogeneic hemopoietic stem cell transplant (ASCT), and specially antibiotics, may be related to increased incidence of graft versus host disease (GVHD) and worst clinical outcomes. Present European Conference on Infections in Leukaemia guidelines exhort to antibiotic treatment optimization in hematological patients, without excluding ASCT receptors. This study aims to demonstrate that in ASCT receptors a predefined protocol of optimization of the antibacterial treatment will preserve the intestinal microbiota diversity which will correlate with decrease incidence of acute GVHD. And that this procedure is safe because it will not worsen the incidence of infections, transplant related mortality, infectious mortality or global survival.
Interventions
PROCEDUREOptimization cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy.
PROCEDUREControl cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics.
Sponsors
Grupo Espanol de trasplantes hematopoyeticos y terapia celular
Instituto de Salud Carlos III
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients admitted to receive their first allogeneic hematopoietic transplant as a treatment of any disease. * Conformity of the patient to participate by signing the informed consent. * Patients who have received a previous autologous transplant are not excluded.
Exclusion criteria
* Non-compliance of the patient to sign the informed consent. * Patients who have already started the conditioning (or thereafter) will not be included. * Allograft recipients who have previously received the transplant will not be included. Second allogeneic transplants are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact on microbiota | From the Previous Day of starting conditioning treatment until the last documented day of antibiotherapy or hospital discharge, whichever came first, assessed up to one month post-transplant. | Comparison of biological alpha and beta diversity of the intestinal microbiota of both study groups (classical and optimized antibiotherapy). Calculation of alpha diversity (OTUs richness and Shannon diversity indexes observed, Faith's Phylogenetic Diversity and Evenness) and beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFra distance, used for comparing biological communities) indexes by QIIME 2 (microbiome bioinformatics platform). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 the groups of patients with high and low diversity in their microbiota. Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test. |
| Transplant related mortality | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | Comparison of transplant related mortality between both study groups (classical and optimized antibiotherapy). Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test. |
| Mortality caused by infection | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | Comparison of infection related mortality between both study groups (classical and optimized antibiotherapy. Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test. |
| Incidence of severe infections | From the day of transplant (Day 0) to Day +30 posttransplant | Comparison of the incidence of severe infections between both study groups (classical and optimized antibiotherapy). Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test. |
| Overall survival | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | Comparison of overall survival between both study groups (classical and optimized antibiotherapy) Kaplan-Meier curve estimation. Test for the comparison of groups: Log-Rank Test. |
| Disease free survival | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | Comparison of the diseae free survival between both study groups (classical and optimized antibiotherapy Kaplan-Meier curve estimation. Test for the comparison of groups: Log-Rank Test. |
Countries
Spain
Outcome results
None listed