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Scientific Calendar March 2026

What is the kappa to lambda ratio, as determined by flow cytometry, in a non-diseased state? 

< 0.3:1 

~ 2:1 

> 3:1 

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Scientific Background

Background

Multiple myeloma (MM) is a plasma-cell neoplasm which arises from the clonal proliferation of malignant plasma cells. Under normal conditions, plasma cells produce antibodies as an immune response to pathogens; in MM, uncontrolled and abnormal growth leads to production of a monoclonal immunoglobulin, which is structurally and functionally similar to an antibody. This excessively produced monoclonal immunoglobulin may be deposited in the bones, the kidneys and the blood, leading to CRAB symptoms such as hypercalcaemia, renal insufficiency, anaemia and bone lesions.

Diagnosis

Diagnosis of multiple myeloma, and monitoring of measurable residual disease (MRD), is performed using several tests:

  1. Flow cytometry of peripheral blood or bone marrow samples to detect abnormal plasma cells.
  2. Bone marrow aspirate or trephine biopsy for cytogenetic analysis and fluorescence in situ hybridisation (FISH).
  3. Measurement of abnormal levels of M protein and beta-2-microglobulin.
  4. Assessment of renal function.
  5. Imaging with PET/CT and MRI.

Immunophenotyping by flow cytometry

Flow cytometry is increasingly used to support diagnosis, classification and MRD monitoring in MM. In diagnostic settings, flow cytometry is used to analyse peripheral blood and bone marrow aspirates to distinguish aberrant clonal plasma cells from normal counterparts based on surface and cytoplasmic antigen expression. Neoplastic plasma cells typically exhibit an aberrant immunophenotype, characterised by bright expression of CD56, CD38 and CD138; reduced or absent expression of CD19 and CD45; and an imbalance in light-chain expression (kappa or lambda).

Case and results

Results of other tests

A routine complete blood count (CBC) on a Sysmex XN-Series analyser revealed platelets (PLT) 41 x 109/L, haemoglobin (HGB) 5.1 mmol/L and instrument flags (IP messages) indicating NRBC, blasts, anisocytosis and thrombocytopenia. Subsequent cell-morphology review revealed 27% plasma cells.

Haematology results

A blood sample was sent to the haematology laboratory where a complete blood count was performed on an XN-Series analyser. The results (Fig. 1) are shown below:

Test Result  

Unit

 
CBC profile      
HGB 5.1 mmol/L  
WBC 9.40 109/L  
PLT-F 41

109/L

 
RBC       2.30

1012/L

 
HCT 0.274

L/L

 
MCV 119.1 fL  
MCH 2,217 amol  
MCHC 186 g/L  
RDW-CV 21.5 %  
White blood cell differential      
NEUT 2.41 109/L 25.7 %
LYMPH 3.14 109/L 33.4 %
MONO 3.73 109/L 39.7 %
EO 0.05 109/L 0.5 %
BASO 0.07 109/L 0.7 %
Important parameters flagged during CBC profile      
WBC RBC

PLT

 
Monocytosis Anisocytosis Thrombocytopenia  
NRBC Present

Macrocytosis

   
Blasts?      

 

Morphology results

The relevant IP messages were verified by morphology (Fig. 2).

Eosinophils - Metamyelocytes -
Basophils - Myelocytes -
Band neutrophils 1% Promyelocytes -
Segmented neutrophils 24% Blasts -
Lymphocytes 39% Plasma cells 27%
Monocytes 9% Erythroblasts 2%

 

Flow cytometric immunophenotyping results

The sample was processed for an MM assay and analysed on the Sysmex XF-1600 flow cytometer. The plots confirmed kappa light-chain restriction of the abnormal plasma cells with the following immunophenotype: positive for CD38, CD138, CD56 and CD81; negative for CD27, CD19 and CD45.

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