Investigation of the Gut Microbiota in Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This cohort study aims to investigate the composition and activity of the gut microbiota of patients newly diagnosed for acute myeloid leukemia (AML), in relationship with their food habits and cachectic hallmarks. The recruitment for this study is currently ongoing with the help of clinicians, nurses and data managers at the Saint-Luc clinics, University Hospital Leuven (Campus Gasthuisberg) and University Hospital Gent. Primary Objective •To assess the composition and activity of the gut microbiota in patients with acute myeloid leukemia (AML) compared to matched control subjects. Secondary Objectives To investigate correlations between the gut microbiota, cachectic hallmarks and gut microbiota-related markers in the blood (gut permeability markers, microbial compounds, microbial metabolites). To characterize the changes in the gut microbial ecosystem that are induced by chemotherapy and associated with colitis. To assess whether the composition of the gut microbiota can predict the severity of chemotherapy-related colitis. Study Design This is an academic multi-centric prospective study. The study is composed of two cohorts (Fig. 1). In Cohort A, patients are included before any chemotherapy. Biological samples (urine, feces, blood) are collected, alongside information on nutritional habits, appetite and medical records. Muscle strength and body composition are also measured. Only patients receiving a standard chemotherapy are included in Cohort B. In Cohort B, biological samples are collected and body composition, muscle strength and appetite are evaluated at 2 different time points, at the end of the chemotherapy (T1) and at discharge (T4).

Official Title
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Investigation of the Gut Microbiota in Patients With Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia, Cachexia

Intervention / Treatment
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* Other: collection of clinical data and biological samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with A diagnosis of AML and related precursor neoplasms according to WHO 2008 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML) Acute leukemia's of ambiguous lineage according to WHO 2008 A diagnosis of refractory anemia with excess of blasts (MDS REAB) 2 and IPSS (International Prognostic Scoring System)-R score > 2. World Health Organization performance status 0, 1 or 2 Sampled bone marrow and/ blood cells at diagnosis with molecular analysis. Written informed consent Good command of the French or Dutch language Exclusion Criteria: Age < 18 years Age > 75 years Pregnancy Antibiotics consumption during the last 30 days before inclusion Recent chemotherapy (< 3 months), with exclusion of hydroxyurea BMI >30 Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance) Gastric bypass Current treatment with antidiabetic or hypoglycemic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haematological patients<br> | Other: collection of clinical data and biological samples<br>* nutritional assessement cachexia symptoms urine, feces and blood samples<br>|
| Active Comparator: Healthy volunteers<br> | Other: collection of clinical data and biological samples<br>* nutritional assessement cachexia symptoms urine, feces and blood samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of gut microbiota composition in patients with acute myeloid leukemia and control subjects | Sequencing DNA extracts from patients' feces (both patients with acute myeloid leukemia and control subjects matched for BMI, sex and age) to obtain the description of gut microbiota composition in those patients | Day 0 i.e.: feces sampling is done at time of diagnosis before any chemotherapy | 
| Measure of metabolites production by the gut microbiota in patients with acute myeloid leukemia and control subjects | 1H-NMR metabolomics performed on patients' feces (both patients with acute myeloid leukemia and control subjects matched for BMI, sex and age) to report the metabolites produced by the gut microbiota of those patients | Day 0 i.e.: feces sampling is done at time of diagnosis before any chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in muscle strength | Measure of muscle strength with Jamar dynamometer (in kg) | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in body composition | Measure of body composition by bio-electric impedance (in kg) | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in appetite | Measure of appetite with the SNAQ questionnaire (score from 5 to 20) | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in gut microbiota-related markers in the blood (gut permeability markers and microbial compounds) | ELISA (in pg/ml) | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in gut microbiota-related markers in the blood (microbial metabolites) | 1H-NMR metabolomics | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in gut microbiota-related markers in urine (gut permeability markers, microbial compounds, microbial metabolites) | ELISA and 1H-NMR metabolomics | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after chemotherapy | Sequencing DNA extracts from patients' feces to obtain the description of gut microbiota composition in those patients. | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in metabolites production by the gut microbiota in patients with acute myeloid leukemia before, during and after chemotherapy. | 1H-NMR metabolomics performed on patients' feces to report the metabolites produced by the gut microbiota of those patients. | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); | 
| Changes in number of participants with treatment related-related adverse events as assessed by CTCAE v4.0 | CTCAE (common terminology criteria for adverse event version 4) | at day 0 (i.e.: feces sampling is done at time of diagnosis before any chemotherapy); |