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

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

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].

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.

Inclusion Criteria:

1. Male or female, 65> =Age (years) >= 18;
2. Newly diagnosed as AML patients according to World Health Organization (WHO) classification;
3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,2;
4. Patients will receive standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy;
5. Patients have not received prior therapy for AML (except hydroxycarbamide);
6. 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);
7. Renal function with creatinine clearance rate (Ccr) higher than 30 ml/min;
8. 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:

1. Acute promyeloid leukemia;
2. AML with central nervous system (CNS) infiltration;
3. Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance) or gastrointestinal surgery;
4. HIV infection, Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment;
5. Severe and active infection that is difficult to control and cannot tolerate induction therapy;
6. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen;
7. Antibiotic exposure within 30 days before enrollment (carbapenems and/or tigecycline were not included, penicillin, cephalosporins and quinolones could be included)
8. Patients reject to participate in the study;
9. Patients with severe heart failure (grade 3-4) or patients deemed unsuitable for enrolment by the investigator.