Blood mNGS for Diagnosing Invasive Pulmonary Fungal Disease in Hematologic Patients

Prospective Multicenter Clinical Study of Blood Microbial Metagenomic Next-Generation Sequencing (mNGS) for the Diagnosis of Invasive Pulmonary Fungal Disease in Patients With Hematologic Diseases

The goal of this clinical trial is to learn whether a blood test called metagenomic next-generation sequencing (mNGS) can help diagnose invasive pulmonary fungal disease in patients with blood disorders. It will also evaluate how accurate this test is compared to traditional methods. The main questions it aims to answer are:

Can blood mNGS accurately identify the fungi causing lung infections?

How well does blood mNGS perform compared to conventional tests (such as culture, serum markers, and imaging)?

Does the mNGS result influence doctors' decisions to start, change, or stop antifungal treatment?

This study is a multicenter, prospective, observational trial. Researchers will compare the mNGS test with standard diagnostic methods to assess its usefulness in early diagnosis of fungal lung infections.

Participants will:

Have a blood sample collected within 72 hours of enrollment for mNGS testing

Undergo routine clinical tests, including imaging, serum markers, and cultures, as part of standard care

Be followed for 42 days to collect information on treatment and clinical outcomes

What is this study about?

This study focuses on patients with blood disorders (such as leukemia, lymphoma, or multiple myeloma) or those who have received a stem cell transplant. These patients are at high risk for developing a serious lung infection caused by fungi, known as invasive pulmonary fungal disease. This infection can be life-threatening if not treated quickly, but it is often difficult to diagnose in its early stages.

Currently, doctors use several methods to look for fungal infections, including CT scans, blood tests for fungal markers, and cultures from lung samples. However, these tests can be slow, sometimes miss the infection, or may not clearly distinguish between infection and other lung problems. In some cases, obtaining a lung sample requires an invasive procedure called bronchoscopy, which can be uncomfortable and carries risks.

What is the new test being studied?

This study is evaluating a new type of blood test called metagenomic next-generation sequencing, or mNGS for short. Unlike traditional tests that look for one specific fungus at a time, mNGS scans the blood for DNA fragments from hundreds of different fungi, bacteria, and other microbes all at once. It works like a powerful search tool that can quickly identify the cause of an infection from a simple blood sample.

Why is this study being done?

The main goal is to find out whether this blood test can accurately diagnose fungal lung infections in high-risk patients. Researchers want to know:

How well does the mNGS test detect fungal infections compared to current standard tests?

Can the test results help doctors start the right antifungal treatment sooner?

Could this blood test reduce the need for more invasive procedures like bronchoscopy?

Who can take part?

The study will enroll patients who:

Have a blood disorder or have received a stem cell transplant

Have a new lung abnormality seen on a CT scan

Are suspected of having a fungal lung infection

Have at least one risk factor for fungal infection, such as a weakened immune system

Participants will be recruited from multiple hospitals across the country.

What happens if someone joins the study?

Participation in the study involves:

A blood sample taken within 72 hours of joining. This sample will be sent to a central lab for mNGS testing. The cost of this first test is covered by the study.

Routine medical care as determined by their own doctor, which may include standard tests such as blood cultures, fungal marker tests, and imaging. If a bronchoscopy is already planned as part of routine care, the fluid from the lungs will also be tested with mNGS at no additional cost.

Follow-up for 42 days. During this time, the research team will collect information about the patient's symptoms, treatments, and test results. No extra visits are required beyond what is already part of standard care.

The mNGS results will not be shared with the treating doctors during the study period, so they will not influence routine care. This allows researchers to fairly compare the new test against standard methods.

What are the potential benefits?

If the study shows that blood mNGS is accurate, it could offer a faster, less invasive way to diagnose fungal lung infections. Early diagnosis may lead to earlier treatment, which could improve outcomes for patients. The study may also help establish clear guidelines for how and when to use this technology in the future.

Are there any risks?

The main risk is that the mNGS test may give results that are not fully accurate, but since these results are not used to guide patient care during the study, there is no direct risk from the test itself. The blood draw involves typical minor discomfort and bruising. All personal health information will be kept confidential.

Who is organizing this study?

The study is led by researchers at Peking University People's Hospital in collaboration with several major medical centers across China. It is supported by a diagnostic laboratory that will perform the mNGS testing.

How long will the study last?

Patient enrollment is expected to take 18 to 24 months, and each participant will be followed for 42 days.

What happens after the study?

The results will help determine whether blood mNGS should become a standard tool for diagnosing fungal lung infections in high-risk patients. If successful, this approach may change clinical practice by enabling earlier, less invasive diagnosis and more targeted treatment.

Inclusion Criteria:

1. Age ≥14 years, gender unrestricted.
2. Patients diagnosed with hematologic malignancies (leukemia, lymphoma, myeloma, etc.) or those who have undergone autologous/allogeneic HSCT.
3. Chest CT confirmed the presence of pulmonary lesions.
4. Clinical suspicion of IFD (with symptoms such as fever, cough, and dyspnea).
5. No other etiological evidence (blood culture, respiratory specimen PCR, etc.) was found.
6. At least one high-risk factor for IFD is present: agranulocytosis (absolute neutrophil count <0.5×10⁹/L), long-term (≥2 weeks) use of glucocorticoids (prednisone equivalent dose ≥0.5 mg/kg/day), concurrent severe acute graft-versus-host disease (GVHD) or moderate-to-severe chronic graft-versus-host disease (cGVHD), cytomegalovirus (CMV) infection or activation, or treatment with T-cell immunosuppressants.
7. Voluntary signing of the informed consent form (or by the legal representative).

Exclusion Criteria:

1. Clinicians determine that the pulmonary lesion is not caused by IFD (e.g., bacterial pneumonia, tumor infiltration, etc.).
2. The patient or his legal representative withdraws the informed consent.
3. Due to severe underlying diseases, mental disorders, etc., the individual has lost the capacity for autonomous signing and lacks a suitable legal representative.