Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio

Amyloid. 2016 Dec;23(4):214-220. doi: 10.1080/13506129.2016.1219715. Epub 2016 Sep 28.

Abstract

Background: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are used for clonal detection in plasma cell dyscrasias, while serum free light chain (sFLC) testing provides quantitation of clonal disease. Up to 20% of patients with light chain (AL) amyloidosis may present with normal FLC ratio (FLCr).

Methods: We assessed the diagnostic, quantitative and prognostic potential of serum heavy light chain ratio (HLCr) in 199 untreated patients at initial evaluation.

Results: An abnormal HLCr was found in 37.2%, abnormal FLCr in 81.9% and positivity by SIFE/UIFE in 94% of patients. HLCr together with SIFE/UIFE identified clonality in 94% patients; the combination with FLCr yielded 100% sensitivity. An HLCr abnormality was significantly over-represented in normal compared to abnormal FLCr group (63.9% versus 31.3%). HLCr did not predict overall survival (OS) (log rank, p = 0.09), while an abnormal FLCr was associated with decreased OS (log rank, p = 0.03). The combined use of both ratios trended toward increased OS in the abnormal HLCr/normal FLCr group (log rank, p = 0.11; Wilcoxon, p = 0.04). On multivariate analysis, HLCr was not predictive of OS, whereas an abnormal FLCr was associated with shorter OS (HR = 1.7, p = 0.04).

Conclusions: The HLC assay has potential as a supplemental test to quantify monoclonal protein in patients with normal FLCr results.

Keywords: AL amyloidosis; Freelite® assay; Hevylite® assay; immunoglobulin heavy light chain.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloidosis / diagnosis*
  • Amyloidosis / immunology
  • Amyloidosis / pathology
  • Clone Cells
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin Heavy Chains / blood
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Light Chains / blood
  • Immunoglobulin Light Chains / genetics*
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Multivariate Analysis
  • Paraproteinemias / diagnosis*
  • Paraproteinemias / immunology
  • Paraproteinemias / pathology
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Prognosis
  • Survival Analysis

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains