Scientists have identified unique compounds in exhaled breath that could help detect blood cancers like lymphoma and leukemia earlier, and non-invasively.
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The study, published in HemaSphere, focused on high-grade lymphoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) to assess these unique compounds.
The researchers found that people with these diseases had distinct volatile organic compound (VOC) profiles that could be detected using a breath sampling device. These molecules are released during normal and abnormal metabolic activity, so they are easily monitored.
Why Breath Matters
Cancer cells undergo metabolic changes that can lead to the production of unusual VOCs. These molecules are often linked to biological processes such as oxidative stress, lipid peroxidation, and ferroptosis.
While past studies have shown that breath VOCs can help identify solid tumors like lung or breast cancer, much less was known about their role in blood cancers. It has been challenging to identify in part because of the complex nature of haematological malignancies and also the difficulty of isolating breath-based biomarkers specific to these diseases.
The current research builds on the idea that lymphoma and leukemia cells may produce distinctive metabolic byproducts, including lipoxidation compounds, that can be identified in the breath.
How the Research was Carried Out
The study included 74 adults: 46 with a blood cancer diagnosis (AML, ALL, or high-grade lymphoma) and 28 healthy volunteers as controls.
Breath samples were collected between August 2020 and March 2022 using the high-sensitivity ReCIVA® breath sampler, part of Owlstone Medical’s Breath Biopsy® platform. This device collects alveolar breath from the lungs in real time while minimizing contamination from the upper airway.
Once collected, the VOCs were isolated through thermal desorption and analysed using gas chromatography-mass spectrometry (GC-MS) with a high-resolution Orbitrap detector. The resulting chemical profiles were compared to reference databases using a software called Compound Discoverer 3.2. Researchers then used statistical methods to identify which compounds were most closely associated with cancer, looking at fold changes, p-values, and diagnostic accuracy based on ROC (receiver operating characteristic) curves.
What They Found
VOC patterns varied by cancer type. In patients with high-grade lymphoma, researchers found higher levels of VOCs associated with lipid peroxidation, particularly alkanes and methylated alkanes. Compounds such as 5-oxotetrahydrofuran-2-carboxylic acid and eucalyptol stood out, with strong ROC-AUC values suggesting good potential for distinguishing patients from healthy individuals.
These findings indicate increased oxidative stress and ferroptosis activity in lymphoma cells, which appear to leave behind a detectable chemical signature in the breath. The researchers also observed consistent changes in sulfur-containing compounds and aldehydes, further evidence of oxidative lipid damage.
In contrast, patients with AML and ALL showed reduced levels of certain molecules, including methanethiol and allyl methylsulfide. These chemicals often come from dietary sources or are produced by gut bacteria, suggesting leukemia may impact metabolism and the microbiome differently than lymphoma. The overall diversity of VOCs in leukemia patients was also lower, potentially reflecting altered systemic oxidative processes or the effects of treatment.
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What It Means
The distinct breath profiles between lymphoma and leukemia patients could indicate the key biological differences in how these cancers develop and affect the body. They also offer a path to earlier, easier diagnosis.
While breath tests are not yet ready for clinical use in blood cancers, this study lays the groundwork for further research. If validated in larger trials, this approach could eventually offer doctors a fast, non-invasive way to screen for disease or monitor treatment response, without imaging or injections.
Next Steps
The researchers suggest that future studies should focus on larger, more diverse patient groups and refine the technology used to detect and interpret VOC patterns. Integrating breath analysis into routine clinical practice will also require standardised protocols and real-world testing.
As sensor technology advances, non-invasive profiling like this could become the new normal, with blood cancers diagnosed earlier and more easily.
Journal Reference
Stiekema L. C. A., et al. (2025). Analysis of volatile organic compounds in exhaled breath of blood cancer patients identifies products of lipid peroxidation as biomarkers for lymphoma detection. HemaSphere, 9, e70168. DOI: 10.1002/hem3.70168, https://onlinelibrary.wiley.com/doi/10.1002/hem3.70168