Evidence map›Paper›PMID 40766049›Full record

ArticleClinical & translational immunology2025

Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia.

Lewis J Williams, Connie Sn Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, Benjamin W Teh

Abstract read
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Article in Clinical & translational immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Lewis J WilliamsThe Walter and Eliza Hall Institute for Medical Research Parkville VIC Australia.
Connie Sn Li-Wai-SuenThe Walter and Eliza Hall Institute for Medical Research Parkville VIC Australia.
Alex L GarnhamThe Walter and Eliza Hall Institute for Medical Research Parkville VIC Australia.
Stefanie M BaderThe Walter and Eliza Hall Institute for Medical Research Parkville VIC Australia.
Constantine S TamThe Alfred Hospital Melbourne VIC Australia.
Ashley WhitechurchDepartment of Clinical Hematology The Royal Melbourne Hospital and Peter MacCallum Cancer Centre Melbourne VIC Australia.
Monica A SlavinDepartment of Infectious Diseases Peter MacCallum Cancer Centre Melbourne VIC Australia.
Marcel DoerflingerThe Walter and Eliza Hall Institute for Medical Research Parkville VIC Australia.
Benjamin W TehDepartment of Infectious Diseases Peter MacCallum Cancer Centre Melbourne VIC Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers. Methods: Patients with relapsed and refractory CLL treated with ibrutinib were evaluated. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals (baseline, 3- and 6 months following commencement of ibrutinib) were analysed, with or without phorbol myristate acetate (PMA)/ionomycin stimulation, using Luminex and RNA sequencing. Luminex and gene expression profiles were compared between patients that who did and did not develop infection to identify immune signatures associated with infection over a subsequent 3-month period. Results: Twenty-eight patients were included in this pilot study. Forty-six per cent of patients developed an infection (13 patients, 17 events) over 9 months of patient monitoring. Most infections were clinically diagnosed (72.7%) with the remainder microbiologically diagnosed bacterial (18.1%) and viral (9.2%) infections. Cell populations did not correlate with subsequent infection. An inflammatory transcriptome profile at 3 months following ibrutinib was associated with a subsequent infection episode. Increased whole protein response to PMA stimulation at 3 and 6 months was associated with subsequent risk for infections. Increased whole protein response to PMA stimulation was associated with subsequent risk of infection 3 months after commencing ibrutinib. Conclusion: The combination of protein and RNA analysis can provide further insight into the interactions of immunotherapies and immunity but should be validated further in large cohorts.

Indexed as

chronic lymphocytic leukaemiaimmunityinfectionpredictionprofilingrisk

Identifiers

PMID40766049
PMCPMC12318685

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.