Investigation of the Gut Microbiota in Acute Myeloid Leukemia Receiving Two Different Induction Therapies

Study Overview
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Brief Summary
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In this observational single-center cohort study, metagenomic Next-Generation Sequencing (mNGS) will be used to investigate the features and changes of gut microbiota in acute myeloid leukemia (AML) patients during the treatment of two different induction therapy regimens [standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy].

Detailed Description
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Infections remain one of the major complications during induction therapy of acute myelocytic leukemia (AML). Previous studies have shown that the variation of gut microbiota was an effective predictor for infection development of AML during induction therapy. A growing number of patients with AML received bcl-2 inhibitor-based targeted induction therapy. The investigators assume that there are different effects of bcl-2 inhibitor-based induction therapy on gut microbiota compared with standard intensive chemotherapy (7+3 regimen). Metagenomic Next-Generation Sequencing (mNGS) will be used to perform the investigation of gut microbiota in AML receiving two different induction therapies. And the relationships of gut microbiota with infection complication will be analyzed.

Official Title
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Investigation of the Gut Microbiota Evaluated by Metagenomic Next-Generation Sequencing (mNGS) in Acute Myeloid Leukemia Receiving Standard Intensive Chemotherapy or Bcl-2 Inhibitor-based Targeted Induction Therapy

Conditions
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Acute Myeloid Leukemia, Adult, Gut Microbiota, Infections

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 65> =Age (years) >= 18; Newly diagnosed as AML patients according to World Health Organization (WHO) classification; Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,2; Patients will receive standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy; Patients have not received prior therapy for AML (except hydroxycarbamide); Liver function: Total bilirubin lower than 3 upper limit of normal (ULN); Aspartate aminotransferase (AST) lower than 3 ULN; Alanine aminotransferase (ALT) lower than 3 ULN (except extramedullary infiltration of leukemia); Renal function with creatinine clearance rate (Ccr) higher than 30 ml/min; Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent. Exclusion Criteria: Acute promyeloid leukemia; AML with central nervous system (CNS) infiltration; Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance) or gastrointestinal surgery; HIV infection, Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; Severe and active infection that is difficult to control and cannot tolerate induction therapy; Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen; Antibiotic exposure within 30 days before enrollment (carbapenems and/or tigecycline were not included, penicillin, cephalosporins and quinolones could be included) Patients reject to participate in the study; Patients with severe heart failure (grade 3-4) or patients deemed unsuitable for enrolment by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Standard intensive chemotherapy<br>Patients with acute myeloid leukemia in this cohort will receive standard induction chemotherapy that combines seven days of cytarabine and three days of anthracycline (7+3 regimen). | Other: collection of biological samples and clinical data<br>* blood and feces samples<br>|
| Bcl-2 inhibitor-based targeted therapy<br>Patients with acute myeloid leukemia in this cohort will receive Bcl-2 inhibitor-based targeted therapy, such as combination of bcl-2 inhibitor plus decitabine/azacitidine with or without sorafenib. | Other: collection of biological samples and clinical data<br>* blood and feces samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy | Sequencing DNA extracts from patients' feces to obtain the description of gut microbiota composition in those patients | Day 0 i.e.: feces sampling is done at time of diagnosis before induction therapy | 
| Changes in metabolites composition of blood in patients with acute myeloid leukemia before, during and after induction therapy | Metabolomics performed on patients' blood to report the metabolites composition in those patients | Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in immune cells of blood in patients with acute myeloid leukemia before, during and after induction therapy | Immunomicin performed on patients' blood to report the composition of immune cells in those patients | Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy | 
| Changes of gut permeability markers and microbial compounds of blood in patients with acute myeloid leukemia before, during and after induction therapy | ELISA (in pg/ml) | Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy | 
| Infection rate during induction therapy | Infection rate of patients with acute myeloid leukemia after two different induction therapy | From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy. | 
| Rate of complete remission | Complete remission after one cycle of induction therapy | From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy. | 
| 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) | From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy. |