Clinical trial NCT05016752: Application of Nanopore Sequencing in Newly Diagnosed Acute Myeloid Leukemia Patients With Bloodstream Infection
Official title: Application of Nanopore Sequencing in Newly Diagnosed Acute Myeloid Leukemia Patients With Neutropenia and Bloodstream Infection: a Prospective Multicenter Observational Clinical Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Blood Stream Infection
Gut Microbiota
Acute Myeloid Leukemia
Keywords: Nanopore sequencing
Blood culture
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-08-23
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed acute myeloid leukemia patients with neutropenia and bloodstream infection

Brief summary: Acute myeloid leukemia (AML) patients are prone to blood stream infection (BSI) due to bone marrow suppression, oral and gastrointestinal mucositis, endovascular tubes, and the application of a large number of broad-spectrum antibiotics. The associated mortality rate is as high as 7.1 %-42%. The use of antibiotics within one hour after the first observation of hypotensive symptoms can guarantee a 79.9% survival rate. For every hour of delay, the patient's survival rate will drop by 7.6%. At present, the blood culture test cycle is long and the positive rate is low. Other infection-related indicators (PCT, CRP) or next-generation sequencing are not highly specific and easy to be misdiagnosed. X-ray, CT and other examinations only have a certain auxiliary value for the infected site. We need new diagnostic tools to accurately identify pathogens. Nano-seq is a next-generation sequencing technology for single-molecule, real-time sequencing and analysis. With ultra-long sequencing read length, it can quickly and accurately identify BSI pathogens types, and give appropriate drug sensitivity results based on drug resistance genes to meet the needs of 99.9% pathogen screening. At the same time, we hope to conduct a prospective evaluation to target high-risk groups of AML prone to BSI in the early stage. The intestine is the body's largest immune organ and the largest reservoir of microbial pathogens. The expansion of certain gut microbiota usually precedes BSI. If there is a correlation between the gut microbiota and MDR-BSI, the colonization and changes of the intestinal flora can be used to predict the risk of BSI in patients during treatment, and preventive measures such as early decolonization or biological intervention will reduce the risk of infection in the future. Combined with Nano-seq and various existing clinical pathogen detection technologies to reduce the occurrence and progress of clinical BSI.

Detailed description: For AML patients with bloodstream infections, we analyzed and compared the sensitivity, specificity, and consistency of Nano-seq and traditional blood culture tests, and evaluated the advantages of Nano-seq for clinical diagnosis and treatment guidance of newly-treated AML bloodstream infections. At the same time, the homology analysis of gut microbiota and bloodstream infection strains was carried out to explore the correlation between gut microbiota and bloodstream infection in newly treated AML patients.

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed AML according to the WHO (2016) classification of acute myeloid leukemia.
* No history of previous chemotherapy or target therapy.
* Neutrophil deficiency (ANC\<0.5x10\^9/L) with the first time fever(Oral temperature \>=38.3 degree C or axillary temperature \>=38.0 degree C) accompanied by chills or hemodynamic instability(BP \<=90/60mmHg）
* Ability to comprehend the investigational nature of the study and provide informed consent.

Exclusion Criteria:

* Patients have a history of chemotherapy or target therapy.
* Patients with other commodities that the investigators considered not suitable for the enrollment.

Primary outcomes:
measure: Sensitivity of Nano-seq group compared to blood culture group
timeFrame: Within 2 week of sampling.
measure: Specificity of Nano-seq group compared to blood culture group
timeFrame: Within 2 week of sampling.
measure: Level of agreement between Nano-seq group and blood culture group
timeFrame: Within 2 week of sampling.
Secondary outcomes:
measure: To compare the detection time, the intensity, duration and cost of antibiotics,length and cost of hospitalization between the Nano-seq group and blood culture group
timeFrame: 3 months
measure: Analyze the homology of the gut microbiota of patients with bloodstream infections and the detected strains
timeFrame: 3 months
measure: Intestinal flora OTU clustering, genus abundance, Alpha diversity, Beta diversity, differences between LEfse groups, baseline value and subsequent changes in the prediction of the metabolic function of the gut microbiota
timeFrame: 3 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Haiping Dai, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: