HEAVY-LIGHT CHAIN IMMUNOASSAYS FOR DIAGNOSIS AND MONITORING IGA MULTIPLE MYELOMA: SAVING PITFALLS ON PROTEIN QUANTIFICATION
(Abstract release date: 05/19/16)
EHA Library. Andrade-Campos M. 06/09/16; 134841; PB1941
Dr. Marcio Andrade-Campos
Contributions
Contributions
Abstract
Abstract: PB1941
Type: Publication Only
Background
Diagnosis and follow-up of Multiple Myeloma (MM) include the assessment of the involved protein named monoclonal component (MC) by serum protein electrophoresis (SPEP) with M-spike densitometry as the gold standard. MC quantification is usually not problematic for patients with IgG MM due to protein characteristics (molar weight, protein charge and migration); however, for IgA MM there are often some difficulties to impossibility their quantification. About 25% of monoclonal gammopathies are IgA subtype; due to the co-migration in alpha or beta area and the presence of IgA dimers, the diagnosis and follow-up is difficult based in the quantification of M-spike using conventional SPEP. The separate determination of intact immunoproteins of monoclonal and polyclonal isotype (heavy/light IgAk/IgAL, HLC) allows quantifying the monoclonal IgA and also assesses immunoparesis status.
Aims
To evaluate the correlation between M-spike concentration by SPE and the quantification by HLC and ratio, and their usefulness as biomarker for early biological relapse detection in IgA MM.
Methods
Every patient with an IgA monoclonal gammopathy, diagnosed of secretory MM according to the criteria for MM diagnosis by the IMWG, and treated in our hospital, was taken in account. The diagnosis and follow-up of monoclonal gammopathies were performed in our Hematology-immunoproteins lab. A chart review was performed collecting: demographic data, clinical stage at diagnosis and protein data: (SPEP, UPE of 24h), quantification of total immunoproteins, inmunofixation (IFX), quantification of FLC, HLC and their ratios (FreeliteTM, HevyliteTM, The Binding Site, Birmingham, UK). Time of study: May 2008-Agosto 2015.
Results
Forty-seven patients were included. Females/males: 23/24; mean age: 67.43 (32-88 years); IgAk: 26 (55.3%); IgAL: 21 (44.7%); 34% of patients had free light chains detectable in urine. A total of 182 protein assessments were registered, 51 present a value of M-spike below 10 g/L, in 62 (34.0%) there were no M-spike by SPEP, but in 39 an abnormal HLCr demonstrated monoclonality confirmed by IFX in 30 samples. The isotype analysis at diagnosis for IgAk patients reveals: mean M-spike concentration 9.61 g/L (0-37.2), HLC-IgAk 24.71 g/L (0.02-63.94), HLC-IgAk minus HLC-IgAL: 24.52 g/L (0-63.94); for IgAL patients shows: mean M-spike concentration 11.4 g/L (0-25.6), HLC-IgAL concentration 17.61 g/L (0.6-41.1), and HLC-IgAL minus HLC-IgAk 16.95 g/L (0.06-41.08). Immunoparesis at diagnosis (abnormal HLC ratio) was present in all patients. In 144 samples with positive MC by SPEP, the mean concentration of M-spike for IgAk samples was 18.43 g/L (1-64.22), HLC-IgAk 22.54 g/L (0.2-109.20), and HLC-IgAk minus HLC-IgAL: 22.51 g/L (0-109.19); and for IgAL samples: 16.2 g/L (1-49.50), HLC-IgAL 20.87 g/L (0.56-55.65), and HLC-IgAL minus HLC-IgAk 20.35 g/L (0.10-55.27). The correlation between both techniques for patients with measurable M-spike for SPEP was excellent, remarking the sensitivity of the HLC (p=0.003 for IgA-k and p<0.001 for IgA-L); the HLCr is a good biomarker for monitoring response.
Conclusion
In this study, 34.0% of SPEP studies in IgA MM do not identify MC, nevertheless more than 50% of them showed monoclonality quantify by HLC-IgA, improving the quantification in cases with low concentrations. The incorporation of this tool for diagnosis and monitoring in IgA MM patients improve the accuracy of follow up. An updated analysis including the value of HLCr in relapse detection will be included in case of acceptance.
Session topic: E-poster
Keyword(s): Assay, Monoclonal gammopathy, Multiple myeloma
Type: Publication Only
Background
Diagnosis and follow-up of Multiple Myeloma (MM) include the assessment of the involved protein named monoclonal component (MC) by serum protein electrophoresis (SPEP) with M-spike densitometry as the gold standard. MC quantification is usually not problematic for patients with IgG MM due to protein characteristics (molar weight, protein charge and migration); however, for IgA MM there are often some difficulties to impossibility their quantification. About 25% of monoclonal gammopathies are IgA subtype; due to the co-migration in alpha or beta area and the presence of IgA dimers, the diagnosis and follow-up is difficult based in the quantification of M-spike using conventional SPEP. The separate determination of intact immunoproteins of monoclonal and polyclonal isotype (heavy/light IgAk/IgAL, HLC) allows quantifying the monoclonal IgA and also assesses immunoparesis status.
Aims
To evaluate the correlation between M-spike concentration by SPE and the quantification by HLC and ratio, and their usefulness as biomarker for early biological relapse detection in IgA MM.
Methods
Every patient with an IgA monoclonal gammopathy, diagnosed of secretory MM according to the criteria for MM diagnosis by the IMWG, and treated in our hospital, was taken in account. The diagnosis and follow-up of monoclonal gammopathies were performed in our Hematology-immunoproteins lab. A chart review was performed collecting: demographic data, clinical stage at diagnosis and protein data: (SPEP, UPE of 24h), quantification of total immunoproteins, inmunofixation (IFX), quantification of FLC, HLC and their ratios (FreeliteTM, HevyliteTM, The Binding Site, Birmingham, UK). Time of study: May 2008-Agosto 2015.
Results
Forty-seven patients were included. Females/males: 23/24; mean age: 67.43 (32-88 years); IgAk: 26 (55.3%); IgAL: 21 (44.7%); 34% of patients had free light chains detectable in urine. A total of 182 protein assessments were registered, 51 present a value of M-spike below 10 g/L, in 62 (34.0%) there were no M-spike by SPEP, but in 39 an abnormal HLCr demonstrated monoclonality confirmed by IFX in 30 samples. The isotype analysis at diagnosis for IgAk patients reveals: mean M-spike concentration 9.61 g/L (0-37.2), HLC-IgAk 24.71 g/L (0.02-63.94), HLC-IgAk minus HLC-IgAL: 24.52 g/L (0-63.94); for IgAL patients shows: mean M-spike concentration 11.4 g/L (0-25.6), HLC-IgAL concentration 17.61 g/L (0.6-41.1), and HLC-IgAL minus HLC-IgAk 16.95 g/L (0.06-41.08). Immunoparesis at diagnosis (abnormal HLC ratio) was present in all patients. In 144 samples with positive MC by SPEP, the mean concentration of M-spike for IgAk samples was 18.43 g/L (1-64.22), HLC-IgAk 22.54 g/L (0.2-109.20), and HLC-IgAk minus HLC-IgAL: 22.51 g/L (0-109.19); and for IgAL samples: 16.2 g/L (1-49.50), HLC-IgAL 20.87 g/L (0.56-55.65), and HLC-IgAL minus HLC-IgAk 20.35 g/L (0.10-55.27). The correlation between both techniques for patients with measurable M-spike for SPEP was excellent, remarking the sensitivity of the HLC (p=0.003 for IgA-k and p<0.001 for IgA-L); the HLCr is a good biomarker for monitoring response.
Conclusion
In this study, 34.0% of SPEP studies in IgA MM do not identify MC, nevertheless more than 50% of them showed monoclonality quantify by HLC-IgA, improving the quantification in cases with low concentrations. The incorporation of this tool for diagnosis and monitoring in IgA MM patients improve the accuracy of follow up. An updated analysis including the value of HLCr in relapse detection will be included in case of acceptance.
Session topic: E-poster
Keyword(s): Assay, Monoclonal gammopathy, Multiple myeloma
Abstract: PB1941
Type: Publication Only
Background
Diagnosis and follow-up of Multiple Myeloma (MM) include the assessment of the involved protein named monoclonal component (MC) by serum protein electrophoresis (SPEP) with M-spike densitometry as the gold standard. MC quantification is usually not problematic for patients with IgG MM due to protein characteristics (molar weight, protein charge and migration); however, for IgA MM there are often some difficulties to impossibility their quantification. About 25% of monoclonal gammopathies are IgA subtype; due to the co-migration in alpha or beta area and the presence of IgA dimers, the diagnosis and follow-up is difficult based in the quantification of M-spike using conventional SPEP. The separate determination of intact immunoproteins of monoclonal and polyclonal isotype (heavy/light IgAk/IgAL, HLC) allows quantifying the monoclonal IgA and also assesses immunoparesis status.
Aims
To evaluate the correlation between M-spike concentration by SPE and the quantification by HLC and ratio, and their usefulness as biomarker for early biological relapse detection in IgA MM.
Methods
Every patient with an IgA monoclonal gammopathy, diagnosed of secretory MM according to the criteria for MM diagnosis by the IMWG, and treated in our hospital, was taken in account. The diagnosis and follow-up of monoclonal gammopathies were performed in our Hematology-immunoproteins lab. A chart review was performed collecting: demographic data, clinical stage at diagnosis and protein data: (SPEP, UPE of 24h), quantification of total immunoproteins, inmunofixation (IFX), quantification of FLC, HLC and their ratios (FreeliteTM, HevyliteTM, The Binding Site, Birmingham, UK). Time of study: May 2008-Agosto 2015.
Results
Forty-seven patients were included. Females/males: 23/24; mean age: 67.43 (32-88 years); IgAk: 26 (55.3%); IgAL: 21 (44.7%); 34% of patients had free light chains detectable in urine. A total of 182 protein assessments were registered, 51 present a value of M-spike below 10 g/L, in 62 (34.0%) there were no M-spike by SPEP, but in 39 an abnormal HLCr demonstrated monoclonality confirmed by IFX in 30 samples. The isotype analysis at diagnosis for IgAk patients reveals: mean M-spike concentration 9.61 g/L (0-37.2), HLC-IgAk 24.71 g/L (0.02-63.94), HLC-IgAk minus HLC-IgAL: 24.52 g/L (0-63.94); for IgAL patients shows: mean M-spike concentration 11.4 g/L (0-25.6), HLC-IgAL concentration 17.61 g/L (0.6-41.1), and HLC-IgAL minus HLC-IgAk 16.95 g/L (0.06-41.08). Immunoparesis at diagnosis (abnormal HLC ratio) was present in all patients. In 144 samples with positive MC by SPEP, the mean concentration of M-spike for IgAk samples was 18.43 g/L (1-64.22), HLC-IgAk 22.54 g/L (0.2-109.20), and HLC-IgAk minus HLC-IgAL: 22.51 g/L (0-109.19); and for IgAL samples: 16.2 g/L (1-49.50), HLC-IgAL 20.87 g/L (0.56-55.65), and HLC-IgAL minus HLC-IgAk 20.35 g/L (0.10-55.27). The correlation between both techniques for patients with measurable M-spike for SPEP was excellent, remarking the sensitivity of the HLC (p=0.003 for IgA-k and p<0.001 for IgA-L); the HLCr is a good biomarker for monitoring response.
Conclusion
In this study, 34.0% of SPEP studies in IgA MM do not identify MC, nevertheless more than 50% of them showed monoclonality quantify by HLC-IgA, improving the quantification in cases with low concentrations. The incorporation of this tool for diagnosis and monitoring in IgA MM patients improve the accuracy of follow up. An updated analysis including the value of HLCr in relapse detection will be included in case of acceptance.
Session topic: E-poster
Keyword(s): Assay, Monoclonal gammopathy, Multiple myeloma
Type: Publication Only
Background
Diagnosis and follow-up of Multiple Myeloma (MM) include the assessment of the involved protein named monoclonal component (MC) by serum protein electrophoresis (SPEP) with M-spike densitometry as the gold standard. MC quantification is usually not problematic for patients with IgG MM due to protein characteristics (molar weight, protein charge and migration); however, for IgA MM there are often some difficulties to impossibility their quantification. About 25% of monoclonal gammopathies are IgA subtype; due to the co-migration in alpha or beta area and the presence of IgA dimers, the diagnosis and follow-up is difficult based in the quantification of M-spike using conventional SPEP. The separate determination of intact immunoproteins of monoclonal and polyclonal isotype (heavy/light IgAk/IgAL, HLC) allows quantifying the monoclonal IgA and also assesses immunoparesis status.
Aims
To evaluate the correlation between M-spike concentration by SPE and the quantification by HLC and ratio, and their usefulness as biomarker for early biological relapse detection in IgA MM.
Methods
Every patient with an IgA monoclonal gammopathy, diagnosed of secretory MM according to the criteria for MM diagnosis by the IMWG, and treated in our hospital, was taken in account. The diagnosis and follow-up of monoclonal gammopathies were performed in our Hematology-immunoproteins lab. A chart review was performed collecting: demographic data, clinical stage at diagnosis and protein data: (SPEP, UPE of 24h), quantification of total immunoproteins, inmunofixation (IFX), quantification of FLC, HLC and their ratios (FreeliteTM, HevyliteTM, The Binding Site, Birmingham, UK). Time of study: May 2008-Agosto 2015.
Results
Forty-seven patients were included. Females/males: 23/24; mean age: 67.43 (32-88 years); IgAk: 26 (55.3%); IgAL: 21 (44.7%); 34% of patients had free light chains detectable in urine. A total of 182 protein assessments were registered, 51 present a value of M-spike below 10 g/L, in 62 (34.0%) there were no M-spike by SPEP, but in 39 an abnormal HLCr demonstrated monoclonality confirmed by IFX in 30 samples. The isotype analysis at diagnosis for IgAk patients reveals: mean M-spike concentration 9.61 g/L (0-37.2), HLC-IgAk 24.71 g/L (0.02-63.94), HLC-IgAk minus HLC-IgAL: 24.52 g/L (0-63.94); for IgAL patients shows: mean M-spike concentration 11.4 g/L (0-25.6), HLC-IgAL concentration 17.61 g/L (0.6-41.1), and HLC-IgAL minus HLC-IgAk 16.95 g/L (0.06-41.08). Immunoparesis at diagnosis (abnormal HLC ratio) was present in all patients. In 144 samples with positive MC by SPEP, the mean concentration of M-spike for IgAk samples was 18.43 g/L (1-64.22), HLC-IgAk 22.54 g/L (0.2-109.20), and HLC-IgAk minus HLC-IgAL: 22.51 g/L (0-109.19); and for IgAL samples: 16.2 g/L (1-49.50), HLC-IgAL 20.87 g/L (0.56-55.65), and HLC-IgAL minus HLC-IgAk 20.35 g/L (0.10-55.27). The correlation between both techniques for patients with measurable M-spike for SPEP was excellent, remarking the sensitivity of the HLC (p=0.003 for IgA-k and p<0.001 for IgA-L); the HLCr is a good biomarker for monitoring response.
Conclusion
In this study, 34.0% of SPEP studies in IgA MM do not identify MC, nevertheless more than 50% of them showed monoclonality quantify by HLC-IgA, improving the quantification in cases with low concentrations. The incorporation of this tool for diagnosis and monitoring in IgA MM patients improve the accuracy of follow up. An updated analysis including the value of HLCr in relapse detection will be included in case of acceptance.
Session topic: E-poster
Keyword(s): Assay, Monoclonal gammopathy, Multiple myeloma
{{ help_message }}
{{filter}}