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Analysis of serum free light chains κ/λ ratio and heavy/light chain pairs of immunoglobulin to the stratification of multiple myeloma according to Mayo Stratification of Myeloma and Revised International Staging System


Authors: Vlastimil Ščudla 1,2;  Jana Balcárková 2;  Pavel Lochman 3;  Miroslava Vincová 2;  Tomáš Pika 2;  Jiří Minařík 2;  Jana Zapletalová 4;  Marie Jarošová 2
Authors‘ workplace: III. interní klinika nefrologická, revmatologická a endokrinologická LF UP a FN Olomouc 1;  Hemato-onkologická klinika LF UP a FN Olomouc 2;  oddělení klinické biochemie FN Olomouc 3;  Ústav lékařské biofyziky LF UP Olomouc 4
Published in: Vnitř Lék 2016; 62(4): 269-280
Category: Original Contributions

Overview

Introduction:
Assessment of serum levels of free light chains (FLC-κ and FLC-λ) and recently heavy/light chain pairs of immunoglobulin (HLC-κ and HLC-λ) and their ratio (FLC-r and HLC-r) has significantly enriched traditional algorithm of multiple myeloma (MM) evaluation. The aim of the presented study was to assess the relationship of classical prognostic parameters of MM, standard FLC-κ/λ and HLC-κ/λ ratio (sFLC-r and sHLC-r), modified ratio of „involved/uninvolved“ FLC and HLC (mFLC-r and mHLC-r ), the difference between „involved – uninvolved“ FLC and HLC (FLC-dif. and HLC-dif.) to current stratification models of MM based on the result of cytogenetic analysis.

Patients and methods:
In a group of 97 patients with MM we assessed serum levels of FLC by FreeliteTM method, and we calculated sFLC-r, mFLC-r and FLC-dif. indices by HevyliteTM method. For cytogenetic analysis we used FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms). For MM stratification we used standard staging systems according to Durie-Salmon (D-S) and International Staging System (ISS) as well as novel stratification systems based on the results of cytogenetic analysis, ie. „Mayo Stratification of Myeloma and Risk-Adapted Therapy“ (mSMART) and „Revised International Staging System“ (R-ISS).

Results:
Stratification mSMART and R-ISS has significantly different representation of „standard“ or „low-risk“ (71, 15.5, 11.3 a 29.9 %), „intermediate risk“ (15.5, 53.6, 34 a 33 %) and „high risk“ patients (13.4, 30.9, 54.7 a 37.1 %) compared to standard staging systems. mSMART stratification was compared to prognostic factors of MM (Hb, albumin, β2-M, creatinine and LDH), and the only significant relationship was found in the case of β2-M, R-ISS had relationship only to Hb and creatinine. In the case of D-S staging we found significant relationship of stages 1–3 and substages A and B to the levels of mFLC-r, FLC-dif. and mHLC-r, ISS had moreover relationship to k HLC-dif. and MIg concentration. Analysis of mSMART stratification showed primarily significant relationship of risk categories 1–3 to mFLC-r and sHLC-r indices, and R-ISS to mHLC-r index and MIg concentration. In both cytogenetics-based stratifications there was a lack of relationship to sFLC-r, FLC-dif. and HLC-dif. indices.

Conclusion:
Comparison of the results of standard staging systems according to D-S and ISS with cytogenetics based models mSMART and R-ISS showed different representation of risk groups, and significantly different relationship to classical prognostic factors together with original relationship of sMART stratification to mFLC-r and sHLC-r, and R-ISS to mHLC-r and MIg concentration.

Key words:
cytogenetic analysis – free light chains ratio – heavy/light chain pairs of immunoglobulin ratio – multiple myeloma – prognostic factors – stratification of multiple myeloma


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