Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio.
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.
a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.
Tatiana
T
Prokaeva
a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.
Brian
B
Spencer
b Boston University School of Public Health , Boston , MA , USA.
Fangui
F
Sun
c The Binding Site, Inc. , San Diego , CA , USA , and.
Richard M
RM
O'Hara
a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.|d Department of Medicine , Section of Hematology and Oncology, Boston Medical Center , Boston , MA , USA.
David C
DC
Seldin
a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.
Lawreen H
LH
Connors
a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.|d Department of Medicine , Section of Hematology and Oncology, Boston Medical Center , Boston , MA , USA.
Vaishali
V
Sanchorawala
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D002999:Clone Cells; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D015999:Multivariate Analysis; D010265:Paraproteinemias / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains
AL amyloidosis; Freelite® assay; Hevylite® assay; immunoglobulin heavy light chain