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. - PowerPoint PPT Presentation

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  • Clinical interpretation of Serum Free Light Chain assays 22 Feb 2013

    Dr. Eric ChanConsultant ImmunologistQueen Mary HospitalHong Kong

  • Figure 3.6. Diagrammatic representation of plasma cells producing intact immunoglobulins with monomeric and dimeric FLC molecules.(Serum Free Light Chain Analysis. AR Bradwell. 5th edition, 2008)

  • Clinical uses of serum free light chain (SFLC) assaysScreening of diseases with monoclonal gammopathySPE (serum protein electrophoresis) + SFLC provide a simple and effective screenCan 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 respectivelyMonitoringLight chain multiple myeloma potentially can replace 24-hour urine light chain quantitationIntact immunoglobulin multiple myeloma for light chain escapeNon-secretory or oligo-secretory multiple myelomaPrognosisMGUS progression (monoclonal gammopathy with unknown significance)IMWG guidelines: Smouldering MM progressionplasmacytoma progressionMyeloma outcomeAL amyloidosis outcomeB-CLL outcomeWald. Macro. outcome

  • 1. LYC (F/59)Breast carcinomaSkull lesion ? Metastasis, biopsy: plasmacytomaBone marrow: plasma cell myeloma, Kappa restrictionSPE, UPE: no monoclonal detected (NMD)IgG, A, M: immunosuppressionSFK , SFL

  • DiscussionQuestions: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.

    1

  • 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/dlIgA 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 MDSerum 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/lS. 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 -- -- -- oligoclonal reconstitution

    DiscussionWeak monoclonal or oligoclonal responses are not uncommon when the bone marrow regenerates after treatment by chemotherapyRaised SFK and SFL, SFLC ratio normalRenal function normal

  • Nov 2006 relapse withsheets of plasma cells in BMBut 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

  • DiscussionDiscrepancy 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-secretory2

  • 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 activationNormal ratio but still SFKAlthough the ratio is normal the elevated SFK levels indicate there is still residual diseaseContinuously falling indicates complete remission3. HWM (M/53)

    21/06/0716/08/0707/01/0826/03/0925/06/0930/09/0912/04/1023/11/10S Free Kappa13,60022.727.721.522.812.011.217.0S Free Lambda3.211.232.024.824.318.318.017.6S K/L Ratio421.532.030.870.870.940.660.620.97urea6.76.73.57.56.75.67.66creatinine219118113125145104110115TreatmentVADPBSCTBM exam pleomorphic plasma cells predominateno p'cytosisregenerating marrowmild p'cytosis

  • "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

  • Discussion: S Free Kappa and S Free Lambda with normal ratio initiallySimilar explanations as beforeContinuously rising S Free Kappa indicates relapseDiscrepancy between serum levels and bone marrowBone marrow negativePET extensive lytic lesions throughout the skeleton3

    07/03/201105/09/201124/10/201126/04/201228/05/201212/10/201212/11/2012S Free Kappa26.134.353.5182.082.0190.0435.0S Free Lambda52.531.426.839.923.517.421.6S K/L Ratio0.51.124.63.510.920.1urea5.66.36.15.110.275.7creatinine109111110111106117102TreatmentthalLen/dxBM examno plasma-cytosisPET ++no plasma-cytosis

  • 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/dlIgA -- 40 L 22 L 27 L 27 L 70 - 386 mg/dlIgM -- 23 L 19 L 14 L 14 L 55 - 307 mg/dlB2M -- 2.56 H -- -- -- < 1.42 ug/mlSPE -- MD MD MD MDSerum 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 myeloma2008-2009 partial remission

  • 4Collect Date : 05/02/09 26/03/09 26/03/09 26/05/09 26/05/09----------------------------------------------------------------------------------------------------------------------------------------IgG -- -- 1190 -- 944 819 - 1725 mg/dlIgA -- -- 89 -- 54 L 70 - 386 mg/dlIgM -- -- 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/LS. Free Lambda -- -- 127H -- 523H 5.71-26.30 mg/LS. Free K/L Ratio -- -- 0.005 -- 0.014

    retrospective assay

    5/2009: Clinical deterioration

  • 4Collect Date : 12/08/09 20/08/09 28/08/09 28/09/09 27/10/09-------------------------------------------------------------------------------------------------------------------