Biochemical profile of Bence-Jones type multiple myeloma.

Multiple myeloma (MM) is a malignant tumor occurring from plasma cells that produce an abnormal monoclonal immunoglobulin - a paraprotein. A distinctive feature of Bence-Jones myeloma is the excretion of monoclonal free light chains of immunoglobulins with 24h urine, and the absence of monoclonal intact immunoglobulins secretion. Comprehensive analysis of biochemical parameters in blood serum and 24h urine in patients with Bence-Jones multiple myeloma using electrophoretic and immunoturbidimetric methods to assess their sensitivity as biomarkers. 50 patients with a morphologically confirmed diagnosis of MM of the Bence-Jones immunochemical type were examined. 28 people without oncological diseases were examinedas a control. Detection of monoclonal secretion in blood serum and daily urine was performed by immunofixation electrophoresis on the Hydrasys 2 electrophoretic system (Sebia). The determination of free light chains of immunoglobulins (FLC) was performed by the immunoturbidimetric method (Binding Site) on an Advia 1800 analyzer (Siemens). Analysis of IgG, IgA, IgM, ß2-microglobulin and C-reactive protein was performed on Cobas 6000 analyzer (Roche). The median excretion of Bence-Jones protein in 24h urine of MM patients was 0.49 g/24h (0.06-2.45 g/24h). In the blood serum, in 86% of cases, the presence of paraproteinemia, represented by κ and λ type light chains of immunogloublins was detected. At the same time, the frequency of detection of monoclonal secretion in blood serum in Bence-Jones type λ myeloma was 95.7%, which was statistically significantly higher than the frequency of detection of monoclonal secretion of type κ - 77.8%. In patients with identified paraproteinemia, Bence-Jones protein excretion in daily urine (median 0.82 g/day) was statistically significantly higher than in patients without a monoclonal component detected in blood serum (median 0.04 g/24h). The levels of FLC in blood serum obtained by immunoturbidimetry in Bence-Jones myeloma of the corresponding type were higher than the reference levels in 100% of cases. The median level of κ-FLC reached 4358 mg/l, λ-FLC - 2225 mg/l, which was statistically significantly higher than the control levels. The median concentrations of IgG, IgA and IgM in patients with Bence-Jones myeloma were statistically significantly lower than in the control group, while the medians of ß2-microglobulin and C-reactive protein were significantly higher than in the control. Our investigation showed high diagnostic efficiency of electrophoretic and immunoturbidimetric analysis of monoclonal secretion in patients with Bence-Jones MM, while FLC analysis demonstrated maximum sensitivity. Bence-Jones MM revealed biochemical signs of secondary immunodeficiency and general inflammatory syndrome.

Immunochemical Diagnosis of Multiple Myeloma.

The diagnostic potentialities of complex immunochemical analysis of the serum and daily urine were evaluated in 118 patients with multiple myeloma. In 95 patients, we observed secretion of monoclonal intact immunoglobulins with heavy chains G (N=69), A (N=19), and M (N=4) and biclonal secretion of paraproteins G and A (N=3). Bence-Jones protein was detected in the sera and daily urine of 16 patients and Bence-Jones proteinuria alone was detected in 3 patients. The diagnostic sensitivity of serum immunoelectrophoresis in multiple myeloma is 94.1%. Analysis of paraproteinuria is particularly important in Bence-Jones myeloma, when paraprotein excretion may be not associated with paraproteinemia. Complex study by immunoelectrophoretic and immunoturbidimetric methods in multiple myeloma increases the diagnostic sensitivity to 99.2%.

[Prognostic value of 1q21 amplification in multiple myeloma]. / Prognosticheskoe znachenie amplifikatsii 1q21 pri mnozhestvennoi mielome.

AIM: To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). SUBJECTS AND METHODS: In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC. Induction therapy with bortezomib-containing cycles was performed. Autologous stem cell transplantation was carried out in 48 patients. The median follow-up of patients was 19.3 months (3.2-77.4 months). Disease progression was diagnosed in 69 (51.5%) patients; 12 patients also underwent FISH study during disease progression. RESULTS: At the onset of MM, amp1q21 was detected in 53 (39.6%) patients. The overall 5-year survival rate in patients with amp1q21 was almost 2 times lower than that in those without amp1q21 (43.5 and 79.4%, respectively; p=0.07). The overall 5-year survival rate in patients with one extra copy of 1q21 (only 3 copies) was 67.3%, that in those with 2 or more extra copies of 1q21 (only 4-7 copies) was 20.9% (p=0.0016). Nine (75%) of the 12 patients examined during disease progression were found to have amp1q21: 2 cases were detected in the period of progression to have amp1q21 in its absence at disease onset; 7 cases had amp1q21 both at MM onset and progression; however, the number of copies of 1q21 was unchanged. CONCLUSION: Аmp1q21 is one of the most common chromosomal abnormalities in patients with new-onset MM and may appear in the course of disease progression. The presence of аmp1q21 is an important prognostic factor and must have to be included in the diagnostic study both at disease onset and progression.

Free Immunoglobulin Light Chains as Criteria of Extracorporeal Hemocorrection in Patients with Monoclonal Gammopathies.

Elimination of free immunoglobulin light chains with the use of EMic2 selective filters was carried out in 12 patients with monoclonal gammopathies and high production of free immunoglobulin light chains. We showed that extracorporeal detoxification for direct removal of excessive free immunoglobulin light chains from the circulation is advisable for these patients, irrespective of the presence and severity of renal insufficiency. Rapid reduction or elimination of free light chains of immunoglobulins in the course of selective extracorporeal elimination helps to prevent the development of irreversible renal failure and to perform adequate antitumor therapy.

Serum immunoglobulin free light chains in patients with monoclonal gammapathies.

Serum concentrations of κ- and λ-free light chains and their ratios were compared in 126 patients with monoclonal gammapathies (age 23-80 years) and 60 normal subjects (25-82 years). The main group included patients with intact immunoglobulin multiple myeloma, Bence Jones multiple myeloma, nonsecreting multiple myeloma, plasmocytoma, and monoclonal gammapathy of unknown origin. The accuracy of the method was evaluated by the analysis of 3 serum specimens with different concentrations of κ- and λ-free light chains. The variability of the method did not surpass the coefficient of variations permissible for this kind of analysis (10%). The new immunochemical method is characterized by high analytical sensitivity 100-fold surpassing that of electrophoretic methods. High concentrations of free light chains were most often found in the sera of patients with multiple myeloma with intact immunoglobulin secretion, Bence Jones multiple myeloma, and plasmocytoma. The diagnostic sensitivity of measurements of serum free light chains by the immunoturbidimetric method attained 90.5%. Combination of this method with serum protein electrophoresis and immunofixation resulted in detection of monoclonal gammapathy in 98.8% cases. These data indicate high specificity and analytical and diagnostic sensitivity of the immunoturbidimetric method for measurement of serum free light chains.