Contributions
Abstract: PB2250
Type: Publication Only
Background
During 2009, Bradwell et al presented a new technique for intact Immunoglobulin Multiple Myeloma (IIMM) and Waldenstrom’s Macroglobulinemia (WM) monitoring. They developed and validated a method for the separate quantification of the kappa and lambda bounded amounts of circulating IgG, IgA and IgM (Heavy/Light Chain-HLC assay). This was achieved by developing antisera with specificity for unique epitopes present at the junction between the heavy and light chains constant regions of each immunoglobulin molecule. This assay allows the quantification of the absolute value of the involved IgGκ, IgGλ, IgAκ, IgAλ, IgMκ and IgMλ along with their deriving ratios (IgGκ/IgGλ etc, Heavy/Light Chain ratio, HLC ratio). According to the literature, these measurements have been proven sensitive and specific for the monitoring of patients with IIMM. Additionally, the prognostic significance of HLC measurements for symptomatic IIMM patients (before treatment initiation) has been investigated. According to the results of two relatively recent studies (Bradwell 2013, Ludwig 2013), extreme low or high HLC ratios (<0.01 or >200) were associated with decreased overall survival of symptomatic IIMM patients.
Aims
The investigation for existence of any prognostic significance of HLC measurements for symptomatic IIMM patients (before treatment initiation) diagnosed and treated in our Hospital’s Hematology and Lymphoma Department.
Methods
Forty-one newly diagnosed symptomatic IIMM patients were studied. Twenty-five of them were men and 16 women. Their median age was 68 years (range: 43-83). The isotype of paraprotein was in 31 cases IgG and in 10 cases IgA. Twenty-four patients were ISS stage I, 13 stage II and four stage III. Patients median follow-up was 16 months (range: 6-24). HLC ratio was determined in all patients before treatment initiation. HLC measurements were performed by using the HevyliteTM assays (The Binding Site Group Ltd, UK) on a SPA PLUS turbidometer.
Results
Statistical analysis was done by using the x2 test. At the time of last evaluation, 36 patients were alive. Five patients had died due to disease progression and their median survival was seven months (range: 2-14). Extreme HLC ratios (<0.01 or >200) emerged in 14 patients (7/31 IgG and 7/10 IgA, p <0.05). Two out of five deceased patients were IgG and three IgA. Also, four out of the five deceased patients had extreme HLC ratios (p <0.05). It is noted that all three IgA deceased patients emerged extreme HLC ratios (p <0.01).
Conclusion
Despite the limited number of patients in our study, it is clear from the above-mentioned that there is a statistically significant correlation between IgA isotype of paraprotein and HLC ratio extreme values (<0.01 or >200). Also, there is a statistically significant correlation between mortality and HLC ratio extreme values, especially for IgA patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma
Abstract: PB2250
Type: Publication Only
Background
During 2009, Bradwell et al presented a new technique for intact Immunoglobulin Multiple Myeloma (IIMM) and Waldenstrom’s Macroglobulinemia (WM) monitoring. They developed and validated a method for the separate quantification of the kappa and lambda bounded amounts of circulating IgG, IgA and IgM (Heavy/Light Chain-HLC assay). This was achieved by developing antisera with specificity for unique epitopes present at the junction between the heavy and light chains constant regions of each immunoglobulin molecule. This assay allows the quantification of the absolute value of the involved IgGκ, IgGλ, IgAκ, IgAλ, IgMκ and IgMλ along with their deriving ratios (IgGκ/IgGλ etc, Heavy/Light Chain ratio, HLC ratio). According to the literature, these measurements have been proven sensitive and specific for the monitoring of patients with IIMM. Additionally, the prognostic significance of HLC measurements for symptomatic IIMM patients (before treatment initiation) has been investigated. According to the results of two relatively recent studies (Bradwell 2013, Ludwig 2013), extreme low or high HLC ratios (<0.01 or >200) were associated with decreased overall survival of symptomatic IIMM patients.
Aims
The investigation for existence of any prognostic significance of HLC measurements for symptomatic IIMM patients (before treatment initiation) diagnosed and treated in our Hospital’s Hematology and Lymphoma Department.
Methods
Forty-one newly diagnosed symptomatic IIMM patients were studied. Twenty-five of them were men and 16 women. Their median age was 68 years (range: 43-83). The isotype of paraprotein was in 31 cases IgG and in 10 cases IgA. Twenty-four patients were ISS stage I, 13 stage II and four stage III. Patients median follow-up was 16 months (range: 6-24). HLC ratio was determined in all patients before treatment initiation. HLC measurements were performed by using the HevyliteTM assays (The Binding Site Group Ltd, UK) on a SPA PLUS turbidometer.
Results
Statistical analysis was done by using the x2 test. At the time of last evaluation, 36 patients were alive. Five patients had died due to disease progression and their median survival was seven months (range: 2-14). Extreme HLC ratios (<0.01 or >200) emerged in 14 patients (7/31 IgG and 7/10 IgA, p <0.05). Two out of five deceased patients were IgG and three IgA. Also, four out of the five deceased patients had extreme HLC ratios (p <0.05). It is noted that all three IgA deceased patients emerged extreme HLC ratios (p <0.01).
Conclusion
Despite the limited number of patients in our study, it is clear from the above-mentioned that there is a statistically significant correlation between IgA isotype of paraprotein and HLC ratio extreme values (<0.01 or >200). Also, there is a statistically significant correlation between mortality and HLC ratio extreme values, especially for IgA patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma