Vnitr Lek 2016, 62(4):269-280

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

Vlastimil Ščudla^1,2,*, Jana Balcárková², Pavel Lochman³, Miroslava Vincová², Tomáš Pika², Jiří Minařík², Jana Zapletalová⁴, Marie Jarošová²

¹ III. interní klinika nefrologická, revmatologická a endokrinologická LF UP a FN Olomouc

² Hemato-onkologická klinika LF UP a FN Olomouc

³ Oddělení klinické biochemie FN Olomouc

⁴ Ústav lékařské biofyziky LF UP Olomouc

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 Freelite^TM method, and we calculated ^sFLC-r, ^mFLC-r and FLC-dif. indices by Hevylite^TM 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.

Keywords: cytogenetic analysis; free light chains ratio; heavy, light chain pairs of immunoglobulin ratio; multiple myeloma; prognostic factors; stratification of multiple myeloma

Received: December 29, 2015; Accepted: January 27, 2016; Published: April 1, 2016  Show citation