Changes in the Gut Microbiota of Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)

Study Overview
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Brief Summary
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COLLECT is a monocentric, prospective, observational study, which aims to assess the association between changes in the intestinal microbiota and the incidence of gastrointestinal graft-versus-host diseases (GvHD). Patients admitted for performance of an allogeneic hematopoietic stem cell transplantation (HSCT) or patients with a first diagnosis of an acute myeloid leukemia (AML) will be enrolled and stool samples will be analyzed using next-generation sequencing. In addition to stool, blood and urine samples will be collected for cytokine and 3-indoxylsulfate analysis. Exposure to drugs will not be influenced and remains at the discretion of the treating physician.

Detailed Description
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Documentation of patient is performed by using the web-based survey platform www.ClinicalSurveys.net which was set up by researchers of the University Hospital of Cologne. This survey platform enables an optimal performance in epidemiological, observational, and interventional trials and is characterized by layered access security and frequent data backup. It has been used for numerous registry and cohort studies with approval of competent authorities and ethics boards. The following data items of patients with a written informed consent are prospectively documented into our database: Demographics Chemotherapeutic agents Other immunosuppressives Radiation treatment Antibiotic prophylaxis and treatment Bowel movement abnormalities HSCT Donor and recipient information Status of hematological disease Days with neutropenia Fever and infectious complications The following samples of patients with a written informed consent are prospectively collected, stored and analyzed: Stool samples (16S rRNA analysis) Urine (3-IS analysis) Ethylenediaminetetraacetic acid (EDTA) blood samples (PBMCs Fluorescence-activated cell sorting (FACS) analysis) Citrate blood samples (cytokine analysis)

Official Title
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Changes Over Time in the Gut Microbiota of High-risk Hematological Patients Undergoing Allogeneic Stem Cell Transplantation (COLLECT)

Conditions
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Acute Myeloid Leukemia, Graft-versus-host-disease, Allogeneic Hematopoietic Stem Cell Transplantation, Stem Cell Transplant Complications

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of at least 18 years Patients admitted for performance of an allogeneic HSCT OR Patients with a first diagnosis of an acute myeloid leukemia No contraindication for an allogeneic stem cell transplantation Subject is not legally incapacitated Written informed consent from the study subject has been obtained Exclusion Criteria: Active inflammatory bowel disease Ongoing gastroenteritis at the time of inclusion Patient has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the patient participating in the study, would make it unlikely for the patient to complete the study, or would confound the results of the study Persons with any kind of dependency on the investigator or employed by the sponsor or investigator Persons held in an institution by legal or official order

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 |
| --- | --- |
| Admitted for allogeneic HSCT<br>Patients admitted for performance of an allogeneic HSCT after high dosis chemotherapy. | |
| First diagnosis AML<br>Patients admitted with a first diagnosis of an acute myeloid leukemia for chemotherapy. Depending on factors like age or molecular risk profile some of these patients will proceed to allogeneic HSCT. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the association between changes in the intestinal microbiota and the incidence of gastrointestinal GvHD | Analyse changes over time in the intestinal microbiota using 16S ribosomal ribonucleic acid (rRNA) analysis and assess microbiota diversity. | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the association between changes in the intestinal microbiota and the incidence of non-relapse mortality | Analyse changes over time in the intestinal microbiota using 16S rRNA analysis and assess microbiota diversity. | 365 days | 
| Investigation of the influence of antibiotics and other risk factors on microbiota changes within this cohort | Analyse changes over time in the intestinal microbiota using 16S rRNA analysis and assess microbiota diversity. | 365 days | 
| Analysis of the association of 3-indoxylsulfate 3-IS in urine/blood with observed microbiota changes | 3-indoxylsulfate (3-IS) concentration levels will be quantified using liquid chromatography in combination with mass spectrometry. | 365 days | 
| Assessment of the effect of microbiota dysbiosis on cytokine and lymphocyte profiles | Cytokine analysis will be performed on the collected plasma samples (citrate) using multiplex assays and read on a Luminex100™ platform. | 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic hematopoietic stem cell transplantation, Graft-versus-host-disease, Acute Myeloid Leukemia