Supervisors: Gab Haeusler, Abby Douglas, Monica Slavin Sponsorship: Kas Thursky

Brief Synopsis: A novel electronic medical record (EMR)-embedded randomised clinical trial comparing early versus late stopping of empirical antibiotics in high-risk haematology patients with fever.

Key Details:

• Conducting a first-of-its-kind adult randomised controlled trial using a novel EMR-embedded trial and data structure with EPIC.
• Assessing both neutropenic and non-neutropenic patients.
• Investigating empiric antibiotic management of fever in high-risk haematology malignancy patients.

For more information, please contact Dr. Abby Douglas.

Synopsis: Clinical suspicion of infection remains a major driver for hospital admissions. However, with the evolution of acute myeloid leukemia (AML) therapies, particularly venetoclax-based treatments, the risk of infection needs to be re-evaluated. This involves a multi-modal clinical approach focused on infection risk screening, delabelling of antibiotic allergies, early infection management, biomarker evaluation, and a febrile neutropenia pathway aimed at home-based care.

Study Objective: Conduct a randomised controlled trial (RCT) of ambulatory neutropenic monitoring versus standard care in a national study of newly diagnosed AML patients on venetoclax and azacitadine.

Key Details:

• ADAPT-ID study: National RCT comparing ambulatory neutropenic monitoring versus standard care.
• New Ven-Aza and HiDAC ambulatory care patients: Novel care pathways for patients at RMH/PMCC.
• Pre-chemo screenings: Optimising infection diagnosis (ID) screening, multidrug-resistant (MDR) screening, and antibiotic allergy assessment.
• Antifungal prophylaxis: In venetoclax and azacitadine patients.
• Frailty and infectious outcomes: Understanding frailty measurements in high-risk patients and their impact on infectious outcomes.
• Health economics: Evaluating the health economics of ambulatory models of care for acute leukemia.
• Remote monitoring: Exploring the role of remote ambulatory monitoring, including options, needs, and readiness assessment.

Suitable for: Medical ID specialists, ambulatory care specialists, haematology nurses, clinical trial researchers, pharmacists, nurse clinicians, nurse practitioner candidates, health services researchers, and allied health professionals.

For more information, please contact A/Prof Michelle Yong.

Evaluate and understand new technological diagnostic assays and biomarkers in immunocompromised hosts.

Objective: Develop Precinct Master Protocol for collection of specimens (blood, urine, CSF) from high-risk ICH patients presenting with fever to better risk stratify them.

Assays for assessment:

• Microbio: Comprehensive molecular testing of blood to identify microbiological pathogens, compared to standard blood culture.
• SeptiCyte RAPID: Blood RNA samples for febrile neutropenic and immunocompromised patients (TGA approved).
• CRISPR-based diagnostic testing: New advancements in gene-editing technology for diagnostics.
• Blood biomarkers: Identifying key biomarkers in blood for early detection of infection.

For more information, please contact A/Prof Michelle Yong.

Synopsis: The World Health Organization (WHO) has identified fungal pathogens as a critical threat to global health, marking them as a priority area for research. Delayed diagnosis of invasive fungal infections (IFI) has been highlighted as a key area of improvement. Early diagnosis is crucial for initiating appropriate antifungal therapy. Currently, rapid detection is hindered by the lack of accessible molecular tests specific to these fungi. Additionally, standard diagnostic methods, including microscopy and culture, are often subject to interpretation and do not effectively assess drug resistance.

Study Goals: Develop and evaluate novel diagnostic assays to improve the rapid detection and management of fungal infections in immunocompromised hosts.

Key Details:

• Develop a multi-centre protocol for the collection of serial whole blood, serum, BAL, body fluids (CSF, vitreous fluid), stool, and urine for evaluating non-culture-based fungal diagnostics and immune profiling in high-risk haematology patients.
• Develop and evaluate a CRISPR-based assay for invasive Aspergillus and resistance to azoles in a single test.
• Assess the feasibility of point-of-care testing for fungal infections.
• Evaluate molecular assays for rare mould infections (e.g., Mucorales) to assess their performance and predictive value.
• Assess the Aspergillus galactomannan Ag VirClia monotest.
• Evaluate urine-based fungal assays for early detection.
• Develop a novel mould molecular assay (Zoe).

For more information, please contact Prof Monica Slavin.

Synopsis: Viral infections following allogeneic haematopoietic stem cell transplantation (alloHSCT) are commonly observed due to significant immune system deficits, particularly in T-cell immunity. A comprehensive viral platform assay (Twist Bioscience) is being utilized to better understand viral burden in patients undergoing allogeneic stem cell transplants, solid organ transplants, and cancer treatments. This platform aims to provide a more detailed understanding of viral epidemiology, resistance, and clinical impacts.

Study Goals: Develop and evaluate a comprehensive viral genotyping platform to assess viral burden and inform patient care in immunocompromised hosts.

Key Details:

• Apply Twist comprehensive viral research panel genomics on cohorts of immunocompromised host (ICH) populations.
• Assess CMV and viral burden in allogeneic haematopoietic stem cell transplant (alloHSCT) recipients using CRESCT samples.
• Evaluate respiratory viral burden in cancer patients using CSMART samples.
• Analyze respiratory samples, including CRISP BAL (bronchoalveolar lavage) samples.
• Develop and validate an assay capable of measuring and quantifying viral loads.
• Evaluate the assay’s ability to detect CMV resistant to wild-type virus strains.
• Explore the cost and feasibility of an assay for monitoring remote or regional patients.
• Develop protocols for new cohorts, including primary immunodeficiencies, CSF samples, kidney transplant patients, and paediatrics.
• Build capacity for conducting viral genotyping assays across multiple sites and patient populations.

For more information, please contact A/Prof Michelle Yong.

Synopsis: The development and delivery of vaccines in high-risk haematology patients is critical to preventing vaccine-preventable infections. This study focuses on identifying the burden of these infections, understanding real-world vaccination uptake, and evaluating immune responses to vaccination in the context of new-generation haematological therapies.

Study Goals: Advance vaccination care and explore immune monitoring strategies to improve patient outcomes in haematological malignancies.

Key Details:

• Advancing vaccination care and delivery for high-risk haematology patients.
• Identifying the burden of vaccine-preventable infections and understanding real-world vaccination uptake through national data-linkage studies.
• Understanding the retention of immunity and response to vaccination in patients undergoing new-generation haematological therapies (prospective study with immune analysis).
• Evaluating new vaccination strategies in a platform randomised trial for patients undergoing autologous haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) therapy.
• Surveying vaccination practices across transplant centres and co-designing an optimal vaccination delivery program.

For more information, please contact Dr. Ben Teh.

Synopsis: Invasive fungal infections (IFI) are rare but often progress to disseminated and fatal outcomes in 30-60% of patients. They represent a significant threat to highly vulnerable groups, including cancer patients, stem cell and solid organ transplant recipients, and those who are critically ill or immunosuppressed. This project aims to address critical evidence gaps in fungal infection epidemiology and optimize treatment strategies.

Study Goals: Improve the understanding and treatment of invasive fungal infections through multicentre studies and clinical trials.

Key Details:

• Conduct multicentre studies on the real-world use of isavuconazole in adult and paediatric patients.
• Develop and optimize a national approach to antifungal therapy.
• Coordinate multicentre CRISP BAL recruitment for fungal infection research.
• Assist in conducting a clinical trial for the infusion of fungal-specific T cells in treatment.
• Evaluate combination antifungal therapies for better treatment outcomes.

For more information, please contact Dr. Zoe Neoh.

Supervisors: Gab Haeusler, Abby Douglas (Possibly ED Supervisor)
Mentors: Karin Thursky, Monica Slavin

Synopsis: Febrile neutropenia (FN) is a common and potentially life-threatening complication in patients with haematological malignancies, particularly those undergoing chemotherapy. The MASCC score, a risk prediction tool for FN, was developed in the era of traditional chemotherapy. This project aims to re-validate and refine the MASCC score in the context of modern therapies, including targeted therapies and immunotherapy, to improve ambulatory management and patient outcomes.

Study Goals: Use big data and large datasets to re-validate the MASCC score and potentially develop a more effective risk prediction model for current-era febrile neutropenia management.

Key Details:

• Re-validate the MASCC score using big data and large datasets in the context of novel therapies and modern FN management.
• Re-calibrate or develop novel, simpler risk prediction scores for FN management in the current clinical era.
• Develop and evaluate a program to allow direct discharge from the emergency department (ED) post-observation for low-risk patients with febrile neutropenia.

Suitable for: Medical ID specialists, ambulatory care medical professionals, nurse clinicians, haematology nurses.

For more information, please contact Dr. Gabrielle Haeusler.

Synopsis: Sepsis is a significant cause of morbidity and mortality in cancer patients, particularly those undergoing intensive treatment such as chemotherapy or stem cell transplantation. This project aims to investigate the long-term impact of sepsis on cancer patients' survivorship, with a focus on developing improved diagnostic tools, identifying biomarkers, and understanding the pathophysiology of sepsis in this vulnerable population.

Study Goals: Evaluate new diagnostic assays, biomarkers, and strategies to improve outcomes for cancer patients who survive sepsis.

Key Details:

• Develop a Precinct Master Protocol for the collection of specimens (blood, urine, CSF) from high-risk immunocompromised host (ICH) patients presenting with fever to risk stratify sepsis.
• Assess various diagnostic assays for detecting sepsis and identifying pathogens in cancer patients:
• Microbio: Comprehensive molecular testing of blood to identify microbiological pathogens, compared to standard blood culture methods.
• SeptiCyte RAPID: Blood RNA testing in febrile neutropenic and immunocompromised patients (TGA approved).
• CRISPR-based diagnostic testing for rapid identification of pathogens.
• Evaluation of blood biomarkers for early sepsis detection and prognosis.

For more information, please contact A/Prof Michelle Yong.

Supervisors: Abby Douglas, Michael Hofman, Monica (Possibly Lisa Guccione or other implementation scientist for PIPPIN extension)
Mentors: Karin Thursky

Synopsis: Nuclear imaging techniques, such as PET (positron emission tomography) and SPECT (single-photon emission computed tomography), have the potential to revolutionize the diagnosis and treatment of infections, especially in immunocompromised patients. This project focuses on evaluating novel nuclear imaging approaches to identify infections early, accurately, and non-invasively, thereby improving patient outcomes and optimizing treatment strategies.

Study Goals: Evaluate and validate nuclear imaging techniques for improved detection and management of infections in immunocompromised patients.

Key Details:

• Assess various diagnostic assays for the detection of infections in immunocompromised patients, including:
• Microbio: Comprehensive molecular testing of blood to identify microbiological pathogens compared to standard blood culture methods.
• SeptiCyte RAPID: Blood RNA testing in febrile neutropenic and immunocompromised patients (TGA approved).
• CRISPR-based diagnostic testing for rapid pathogen identification.
• Blood biomarkers for the detection and monitoring of infections.

For more information, please contact A/Prof Michelle Yong.