From the Guidelines
To test for light chains in blood when evaluating a bone marrow disorder, I recommend ordering a serum free light chain assay (SFLC). This test measures the levels of kappa and lambda free light chains in the blood and calculates the kappa/lambda ratio. The normal reference ranges are approximately 3.3-19.4 mg/L for kappa, 5.7-26.3 mg/L for lambda, and 0.26-1.65 for the ratio, though these may vary slightly between laboratories.
Key Points to Consider
- The serum free light chain assay is more sensitive than traditional protein electrophoresis for detecting small amounts of light chains and is especially valuable for monitoring patients with light chain-only disease.
- The test works because in plasma cell disorders, there is often overproduction of either kappa or lambda light chains, disrupting the normal ratio.
- An abnormal ratio indicates clonal plasma cell proliferation, while elevated levels of both light chains with a normal ratio typically suggest kidney dysfunction rather than a bone marrow disorder.
- According to the most recent guidelines, including those from 1, the serum FLC assay is a crucial component of the initial diagnostic workup for multiple myeloma and related plasma cell disorders, providing high sensitivity and prognostic value.
- It is essential to use the same test for serial studies to ensure accurate relative quantification of the myeloma or M-protein, as noted in 1 and 1.
- The FLC ratio is required for documenting stringent complete response according to the International Myeloma Working Group Uniform Response Criteria, as mentioned in 1 and 1.
From the Research
Blood Testing for Bone Marrow Disorder
To test for light chain in blood for a bone marrow disorder, the following options are available:
- Serum immunoglobulin-free light chain (FLC) assay, which measures levels of free kappa and lambda immunoglobulin light chains 2
- Serum protein electrophoresis (SPE) in combination with serum immunofixation electrophoresis (IFE) and urine protein electrophoresis (UPE) 3, 4
- Serum-free light chain assay (sFLC) using kits such as Siemens N Latex FLC kits 5
Test Selection
The choice of test depends on the specific clinical context and the type of plasma cell disorder suspected:
- For screening, the serum FLC assay in combination with SPE and IFE yields high sensitivity 2
- For diagnosis and monitoring of plasma cell disorders, the combination of SPE and sFLC has the highest sensitivity and accuracy index 6
- For monitoring residual disease, SPE and UPE can be used to screen patients, and negative results can obviate the need for bone marrow biopsy 4
Key Considerations
When interpreting test results, it is essential to consider the following:
- The serum FLC assay has limitations, and results should be interpreted with caution 3
- The kappa/lambda ratio should be considered in the context of the individual patient's clinical presentation 3, 5
- Further tissue or bone marrow biopsy may be needed in patients with unexplained bone lesions and an abnormal sFLC kappa/lambda ratio, even if serum and urine IFE results are negative 5