Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors

Study Overview
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Brief Summary
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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.

Official Title
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Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors: Impact on Intestinal Microbiota and in Clinical Outcomes

Conditions
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Hematopoietic Stem Cell Transplantation, Graft Versus Host Disease

Intervention / Treatment
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* Procedure: Optimization cohort
* Procedure: Control cohort


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control cohort<br>Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics. | Procedure: Control cohort<br>* Recipients of an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics.<br>|
| Optimization cohort<br>Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy. | Procedure: Optimization cohort<br>* Recipients of an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact on microbiota | 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). | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 the groups of patients with high and low diversity in their microbiota. Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test. | From the day of transplant (Day 0) to Day +100 posttransplant | 
| Transplant related mortality | 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. | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | 
| Mortality caused by infection | 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. | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | 
| Incidence of severe infections | 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. | From the day of transplant (Day 0) to Day +30 posttransplant | 
| Overall survival | 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. | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | 
| Disease free survival | 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. | From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, microbiome, graft versus host disease, infection, antibiotics