Non-Hodgkin’s lymphoma (NHL) is a type of cancer that starts in the white blood cells called lymphocytes, which are part of the body’s immune system. NHL can occur at any age and is one of the most common cancers in the US. Detecting NHL as early as possible is critical for effective treatment and improved prognosis. Medical researchers are investigating whether blood tests can reliably detect NHL.
What is non-Hodgkin’s lymphoma?
Non-Hodgkin’s lymphoma is a cancer that originates in the lymphocytes or white blood cells. Lymphocytes are part of the body’s infection-fighting immune system. There are two major types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). B cells produce antibodies to combat infections while T cells destroy infected or cancerous cells.
In NHL, lymphocytes transform and multiply uncontrollably, forming malignant tumors in the lymph nodes, spleen, bone marrow and other organs. NHL has many subtypes, but the two main categories are B-cell lymphomas and T-cell lymphomas. Common subtypes include diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma.
NHL is the seventh most common type of cancer in the US. According to the American Cancer Society, about 77,240 new cases of NHL will be diagnosed in the US in 2022. NHL accounts for about 4% of all cancers and is more common in men than women. The overall 5-year survival rate for NHL is 73%. However, survival rates can vary significantly depending on NHL subtype and stage at diagnosis.
What are the symptoms of non-Hodgkin’s lymphoma?
The signs and symptoms of NHL depend on the location of the cancer, but may include:
- Enlarged, painless lymph nodes in the neck, armpits or groin
- Abdominal pain or swelling
- Chest pain, coughing or trouble breathing
- Persistent fatigue
- Fever
- Night sweats
- Unexplained weight loss
However, many symptoms of NHL are vague and similar to those of infections or other benign conditions. NHL symptoms also vary based on the subtype. Follicular lymphoma, for example, tends to progress slowly with few obvious symptoms initially.
Why early detection of NHL is important
Detecting NHL in its early stages leads to better treatment outcomes. When diagnosed and treated early, the 5-year relative survival rate for NHL is 71%. But this drops to just 63% when it has already reached stage III or IV. Advanced NHL is harder to treat successfully.
Early diagnosis also allows doctors to prescribe less aggressive chemotherapy regimens with fewer side effects. It improves chances of achieving complete remission. In contrast, people diagnosed with late stage aggressive NHL often need stronger multi-drug chemotherapy and radiation.
Annual screening in high-risk groups using blood tests may help identify NHL before symptoms develop. This approach improves rates of early stage diagnosis. It also reduces NHL mortality and improves overall survival.
How is non-Hodgkin’s lymphoma currently diagnosed?
Currently, doctors use imaging tests and biopsies to diagnose NHL. Common diagnostic tests include:
- Imaging tests like CT scan, PET scan, MRI or ultrasound to look for enlarged lymph nodes or tumors in the body.
- Biopsy of enlarged lymph node or mass to examine cells under a microscope.
- Bone marrow biopsy to check for lymphoma in the bone marrow.
- Lumbar puncture to test cerebrospinal fluid if lymphoma is suspected in the brain or spinal cord.
These procedures are invasive, expensive and involve radiation exposure. Imaging can also fail to detect tumors under 1-2 cm in size. Doctors may prescribe chemotherapy just based on PET scan results, before confirming NHL with a lymph node biopsy.
Potential benefits of blood tests for non-Hodgkin’s lymphoma screening
A simple, low-cost blood test to screen for NHL could:
- Allow earlier diagnosis and treatment of NHL for improved outcomes.
- Reduce need for lymph node biopsies to diagnose low-grade NHL.
- Enable regular NHL screening for high-risk groups like people with autoimmune disorders.
- Help monitor NHL treatment progress with serial blood tests.
- Provide a specific NHL biomarker profile unique to each subtype.
- Indicate NHL recurrence through detection of circulating lymphoma cells.
However, major challenges remain before blood tests can definitively screen for or diagnose NHL.
Technical challenges with developing a lymphoma blood test
There are some key difficulties researchers still need to overcome to develop accurate blood tests for NHL detection and diagnosis:
- NHL is not one disease but many subtypes, so a single marker cannot screen for all NHL.
- Overlap between NHL biomarkers and normal physiological processes makes specificity difficult.
- NHL biomarkers may be present at very low concentrations in blood and challenging to detect.
- Some biomarkers are released by both NHL and benign conditions, reducing test accuracy.
- NHL biomarkers can fluctuate with disease activity and during therapy.
No NHL blood test biomarkers or assays so far reliably distinguish between NHL subtypes or benign lymph node enlargement. However, progress is being made to overcome these limitations.
Promising non-Hodgkin’s lymphoma blood biomarkers
Researchers have identified several promising protein and genetic biomarkers detectable in the blood that may aid NHL detection and monitoring in future.
Protein biomarkers
- Beta-2 microglobulin (B2M) – Elevated in 40-60% of B-NHL cases.
- Soluble interleukin-2 receptor (sIL-2R) – Elevated in >80% of B-NHL cases.
- Free light chains (FLC) – Monoclonal FLC production seen in many B-NHLs.
- Fibrinogen – Increased in multiple myeloma and some NHLs.
Genetic biomarkers
- Cell-free circulating tumor DNA – Can detect lymphoma-specific DNA mutations.
- Cell-free circulating RNA – Measures lymphoma gene expression patterns.
- MicroRNAs – NHL exhibits specific miRNA signatures.
Researchers are also developing antibody-based assays and combining multiple protein biomarkers to improve NHL detection accuracy.
Ongoing research into NHL blood tests
Many research teams worldwide are actively investigating blood tests for NHL screening, diagnosis and post-treatment monitoring. Some examples include:
- A 2019 Japanese study developed a blood test using 5 proteins plus age to detect NHL with 87% accuracy.
- Scientists at Stanford University are using next-generation sequencing of cell-free DNA to detect follicular lymphoma.
- Researchers at Roswell Park Cancer Institute have identified a small RNA signature in blood specific to diffuse large B-cell lymphoma.
- The UK-based CANCER-ID consortium is analyzing blood biomarkers in lymphoma using mass spectrometry.
Ongoing advances in genomics, proteomics, microfluidics and machine learning will enable more accurate NHL blood tests. But extensive clinical validation is still needed before they gain FDA approval and widespread use.
Are blood tests for non-Hodgkin’s lymphoma approved for clinical use?
Currently, there are no definitive blood tests to either screen for or diagnose NHL approved for clinical practice. However, elevated LDH, B2M, sIL-2R and FLC can provide supportive information to doctors investigating for possible NHL.
The first prognostic blood test specifically for one type of NHL called diffuse large B-cell lymphoma (DLBCL) was FDA approved in 2020. This test measures the levels of circulating tumor DNA in the blood after initial chemotherapy. It helps identify patients at low or high risk for DLBCL progression to guide further treatment decisions.
While research continues, tissue biopsies to examine lymph node architecture and cytogenetics remain the gold standard for NHL diagnosis. Blood tests may eventually allow straightforward screening and monitoring, but cannot yet definitively diagnose specific NHL subtypes.
Using current NHL blood tests
Despite limitations, abnormal blood test results may prompt further NHL investigation with imaging and biopsy. Doctors can use blood tests in NHL as follows:
- Screening high-risk groups – Test sIL-2R, B2M, FLC levels.
- Supporting NHL diagnosis – Test LDH, ESR, blood counts, FLC, albumin, B2M.
- Determining prognosis – Test LDH, ESR, albumin, B2M, stage.
- Monitoring treatment – Test LDH, ESR, blood counts, sIL-2R.
Repeat testing allows tracking of biomarker trends and lymphoma progress. However, normal results do not conclusively rule out NHL. Clinical correlation with other symptoms is essential for interpreting any NHL blood test results.
Conclusion
Early NHL detection and treatment significantly improves patient outcomes and survival rates. Researchers worldwide are actively investigating blood-based assays that can accurately and reliably screen for NHL or detect recurrence after treatment.
However, tissue biopsy remains essential to confirm NHL diagnosis and determine the exact lymphoma subtype. While promising, NHL blood tests are currently experimental and not yet ready for clinical diagnostic use.
Simple, accurate blood tests would be a game-changer for NHL screening and treatment monitoring. But major technical hurdles around sensitivity and specificity remain. Extensive clinical validation in large NHL patient cohorts is needed before they will be approved for widespread medical use.