Non-Hodgkin’s lymphoma (NHL) is a complex group of blood cancers originating mainly from lymphocytes, a type of white blood cell. Monitoring the disease’s progression and response to treatment traditionally relies heavily on biopsies—procedures where tissue samples are taken from lymph nodes or other affected sites for microscopic examination. However, biopsies are invasive, sometimes painful, and not always feasible for frequent monitoring. This has led to growing interest in whether blood biomarkers—measurable substances in the blood—can replace biopsies in NHL monitoring.
Blood biomarkers are molecules or cells in the bloodstream that reflect the presence, activity, or burden of cancer. They offer a less invasive, more convenient way to track disease status. In NHL, several types of blood biomarkers have been studied, including soluble proteins, circulating tumor DNA (ctDNA), and specific immune cell markers. The question is whether these biomarkers can provide the same depth and reliability of information as biopsies.
Biopsies provide direct access to tumor tissue, allowing detailed analysis of lymphoma subtype, genetic mutations, and microenvironment. This information is crucial for diagnosis, prognosis, and treatment planning. Blood biomarkers, by contrast, offer indirect evidence of disease. For example, elevated levels of soluble interleukin-2 receptor (sIL-2R) in the blood have been linked to lymphoma activity and can help monitor treatment response. Similarly, lactate dehydrogenase (LDH) and alkaline phosphatase levels sometimes correlate with tumor burden or aggressiveness. These markers are useful but nonspecific and can be influenced by other conditions.
More recently, advances in molecular techniques have enabled detection of circulating tumor DNA—fragments of DNA shed by lymphoma cells into the bloodstream. ctDNA can carry genetic mutations characteristic of the lymphoma, allowing for a form of “liquid biopsy.” This approach can track minimal residual disease (small numbers of cancer cells remaining after treatment) and detect early relapse. For example, in chronic lymphocytic leukemia (CLL), a subtype of NHL, researchers have identified PD-1 expression on proliferating lymphoma cells in blood samples, which correlates with disease activity and response to targeted therapies. This suggests blood-based markers can provide dynamic insights into tumor biology without invasive procedures.
Despite these promising developments, blood biomarkers currently cannot fully replace biopsies in NHL monitoring. Biopsies remain essential for initial diagnosis and for cases where disease behavior changes or resistance to therapy develops. Blood biomarkers often lack the specificity and sensitivity to capture the full complexity of lymphoma subtypes or to detect localized disease that does not shed sufficient markers into the bloodstream. Moreover, some biomarkers can be elevated due to non-cancerous conditions, complicating interpretation.
The future of NHL monitoring likely involves integrating blood biomarkers with imaging and clinical assessment to reduce reliance on biopsies. For example, PET/CT scans combined with serial blood biomarker measurements can provide a comprehensive picture of disease status. Molecular profiling of ctDNA may guide personalized treatment adjustments in real time. However, standardization of biomarker assays, validation in large patient cohorts, and understanding of biomarker kinetics are needed before blood tests can replace tissue biopsies.
In summary, blood biomarkers hold great promise as minimally invasive tools for monitoring non-Hodgkin’s lymphoma, especially for tracking treatment response and detecting relapse. They can complement but not yet fully substitute for biopsies, which remain the gold standard for detailed diagnosis and assessment. Ongoing research is rapidly advancing the field, moving toward a future where blood-based monitoring could significantly reduce the need for invasive procedures while maintaining clinical accuracy and patient safety.
