Clinical interpretation of serum free light chain assays
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Clinical interpretation of Serum Free Light Chain assays. 22 Feb 2013 Dr. Eric Chan Consultant Immunologist Queen Mary Hospital Hong Kong. Figure 3.6. Diagrammatic representation of plasma cells producing intact immunoglobulins with monomeric κ and dimeric λ FLC molecules.

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Clinical interpretation of Serum Free Light Chain assays

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Clinical interpretation of serum free light chain assays

Clinical interpretation of Serum Free Light Chain assays

22 Feb 2013

Dr. Eric Chan

Consultant Immunologist

Queen Mary Hospital

Hong Kong


Clinical interpretation of serum free light chain assays

Figure 3.6. Diagrammatic representation of plasma cells producing intact immunoglobulins with monomeric κ and dimeric λ FLC molecules.

(Serum Free Light Chain Analysis. AR Bradwell. 5th edition, 2008)


Clinical uses of serum free light chain sflc assays

Clinical uses of serum free light chain (SFLC) assays

  • Screening of diseases with monoclonal gammopathy

    • SPE (serum protein electrophoresis) + SFLC provide a simple and effective screen

    • Can replace SPE+UPE (urine protein electrophoresis)

    • UPE and serum IFE (immunofixation) can be ordered more selectively e.g. for amyloidosis and for typing of myeloma respectively

  • Monitoring

    • Light chain multiple myeloma – potentially can replace 24-hour urine light chain quantitation

    • Intact immunoglobulin multiple myeloma – for light chain escape

    • Non-secretory or oligo-secretory multiple myeloma

  • Prognosis

    • MGUS progression (monoclonal gammopathy with unknown significance)

    • IMWG guidelines:

      • Smouldering MM progression

      • plasmacytoma progression

      • Myeloma outcome

      • AL amyloidosis outcome

      • B-CLL outcome

      • Wald. Macro. outcome


1 lyc f 59

1. LYC (F/59)

  • Breast carcinoma

  • Skull lesion ? Metastasis, biopsy: plasmacytoma

  • Bone marrow: plasma cell myeloma, Kappa restriction

  • SPE, UPE: no monoclonal detected (NMD)

  • IgG, A, M: immunosuppression

  • SFK ↑, SFL ↓


Discussion

Discussion

1

  • Questions:

    • Mis-match between UPE and SFLC?

    • Light-chain Myeloma or Non-secretory Myeloma?

  • High SFK levels may be due to polymerisation. This results in an over-estimation of the SFK level. Polymerisation would also cause a false negative result in UPE because the polymerised proteins are of different charges.

  • By definition this is non-secretory myeloma. There has been no modification of the definition which is based on SPE/UPE/IFX. But this patient is more likely to have LCMM.


2 cky m 58

2. CKY (M/58)

  • June 2005 – diagnosed Lambda light chain myeloma

    • BM - markedly hypercellular marrow for age. Sheets of abnormal plasma cells are seen.

  • Jan 2006 – post BMT BM: residual myeloma

    Collect Date : 29/06/05 02/07/05 03/07/06 30/07/06 14/08/06

    ------------------------------------------------------------------------------------------------------------------------------

    IgG 633 L -- 767 L 776 L 1030 819 – 1725 mg/dl

    IgA 61 L -- 133 111 136 70 - 386 mg/dl

    IgM 29 L -- 68 86 156 55 - 307 mg/dl

    SPE Weak MD -- NMD weak MD weak MD

    Serum IFX free L -- -- weak GK

    Total protein 66 -- -- 51.0 61.0 g/l

    % Paraprotein 3 -- -- 4.2 5.2 %

    Paraprotein 2 -- -- 2.1 3.2 g/l

    S. Free Kappa -- -- -- -- 21.90 H 3.30-19.40 mg/l

    S. Free Lambda -- -- -- -- 61.90 H 5.71-26.30 mg/l

    S. K/L Ratio -- -- -- -- 0.35 0.26-1.65

    UPE -- MD -- -- --

    Urine IFX -- FL -- -- --

    Urine protein -- 0.47 -- -- -- <0.15 g/D

    Urine % paraprotein -- 21% -- -- --

  • Jul 2006 – weak IgG/K band -> oligoclonal reconstitution

  • Discussion

    • Weak monoclonal or oligoclonal responses are not uncommon when the bone marrow regenerates after treatment by chemotherapy

    • Raised SFK and SFL, SFLC ratio normal

    • Renal function normal


Clinical interpretation of serum free light chain assays

Nov 2006 – relapse with

sheets of plasma cells in BM

But SFLC mildly elevated and UPE weak

Trephine biopsy shows markedly hypercellular marrow diffusely infiltrated by abnormal plasma cells. Many show nuclear immaturity and prominent nucleoli. Little erythroid and myeloid activity are recognised. Megakaryocytes are not seen. Bony trabeculae are unremarkable. Reticulin fibres are moderately coarsened.

2


Discussion1

Discussion

2

  • Discrepancy between bone marrow and serological findings (weak SPE or UPE bands, low SFLC levels, but marked immunosuppression)

  • In general paraprotein levels reflect tumour load.

  • The tumour cells of this patient is oligo-secretory


Clinical interpretation of serum free light chain assays

3. HWM (M/53)

  • Questions & Discussion:

    • Reasons of ↑ SFK and SFL

      • There is a mild degree of renal impairment. Hence both SFK and SFL are elevated.

      • Other causes: polyclonal activation

    • Normal ratio but still ↑SFK

      • Although the ratio is normal the elevated SFK levels indicate there is still residual disease

      • Continuously falling indicates complete remission


Clinical interpretation of serum free light chain assays

"Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure" BMC Nephrology 2008;9:11 doi: 10.1186/1471-2369-9-112


Clinical interpretation of serum free light chain assays

3

  • Discussion:

    • ↑ S Free Kappa and S Free Lambda with normal ratio initially

      • Similar explanations as before

      • Continuously rising S Free Kappa indicates relapse

    • Discrepancy between serum levels and bone marrow

      • Bone marrow negative

      • PET – extensive lytic lesions throughout the skeleton


4 light chain escape twf

4. Light chain escape (TWF)

Collect Date : 26/10/07 26/10/07 06/12/07 26/12/07 15/01/08

------------------------------------------------------------------------------------------------------------------------------

IgG -- 4870 H 1580 853 880 819 - 1725 mg/dl

IgA -- 40 L 22 L 27 L 27 L 70 - 386 mg/dl

IgM -- 23 L 19 L 14 L 14 L 55 - 307 mg/dl

B2M -- 2.56 H -- -- -- < 1.42 ug/ml

SPE -- MD MD MD MD

Serum IFX -- GL -- -- --

Total protein -- 100.0 68.0 61.0 68.0 g/l

% Paraprotein -- 27.5 18.8 9.9 8.3 %

Paraprotein -- 27.5 12.8 6.0 5.6 g/l

UPE MD -- -- -- --

Urine IFX FL -- -- -- --

%Parapro.(Ur) 14.5 -- -- -- -- %

2007 – present as IgG myeloma

2008-2009 – partial remission


Clinical interpretation of serum free light chain assays

4

Collect Date : 05/02/09 26/03/09 26/03/0926/05/09 26/05/09

----------------------------------------------------------------------------------------------------------------------------------------

IgG -- -- 1190 -- 944 819 - 1725 mg/dl

IgA -- -- 89 -- 54 L 70 - 386 mg/dl

IgM -- -- 97 -- 59 55 - 307 mg/dl

SPE -- -- WMD -- NMD

% Paraprotein -- -- WQ -- -- %

UPE NMD NMD -- MD --

%Parapro.(Ur) -- -- -- 44.1 -- %

S. Free Kappa -- -- 0.64 -- 7.44 3.30-19.40 mg/L

S. Free Lambda -- -- 127H -- 523H 5.71-26.30 mg/L

S. Free K/L Ratio -- -- 0.005 -- 0.014

retrospective assay

5/2009: Clinical deterioration


Clinical interpretation of serum free light chain assays

4

Collect Date : 12/08/09 20/08/09 28/08/09 28/09/09 27/10/09

-------------------------------------------------------------------------------------------------------------------------

IgG -- -- 646 L 521 L 394 L 819 - 1725 mg/dl

IgA -- -- 24 L 18 L 10 L 70 - 386 mg/dl

IgM -- -- 28 L 21 L 15 L 55 - 307 mg/dl

SPE -- -- MD MD MD

Total protein -- -- 79.0 68.0 64.0 g/l

% Paraprotein -- -- 3.0 3.0 2.1 %

Paraprotein -- -- 2.4 2.0 1.3 g/l

UPE MD -- -- -- --

%Parapro.(Ur) 88.2 -- -- -- -- %

S. Free Kappa -- -- -- 6.86 -- 3.30-19.40 mg/L

S. Free Lambda -- -- -- 5790 -- 5.71-26.30 mg/L

S. K/L Ratio -- -- -- 0.0012 --

IgG paraprotein levels stable

UPE & SFL increasing


Clinical interpretation of serum free light chain assays

4

Collect Date : 05/07/10 05/07/10 05/07/10 19/07/10 23/07/10

------------------------------------------------------------------------------------------------------------------------------

IgG -- 267 L -- 445 L 448 L 819 - 1725 mg/dl

IgA -- 14 L -- 35 L 37 L 70 - 386 mg/dl

IgM -- 8 L -- 23 L 21 L 55 - 307 mg/dl

S. Free Kappa -- -- <1.07 -- -- 3.30-19.40 mg/L

S. Free Lambda -- -- >3000.00 H -- -- 5.71-26.30 mg/L

S. K/L Ratio -- -- <0.0004 -- --

SPE -- WMD -- WMD WMD

Total protein -- 54.0 -- 67.0 61.0 g/l

% Paraprotein -- 1.2 -- 2.4 2.7 %

Paraprotein -- 0.6 -- 1.6 1.6 g/l

UPE MD -- -- -- --

%Parapro.(Ur) 69.0 -- -- -- -- %

SFL continuously ↑ → death (2010)


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