The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48.0 and 23.3 months, respectively. According to the presence of amp(1q21), t(4;14)(p16;q32), and del(17p13) and the International Staging System (ISS), we stratified patients into low-risk, intermediate-risk and high-risk groups. A median PFS was 52.9, 25.6, and 10.0 months, respectively; a median OS was not reached, 64.0 and 25.0 months, respectively. In conclusion, our study confirmed the prognostic value of cytogenetic changes and showed that prognostic models based on ISS and cytogenetic studies should include not only del(17p13) and t(4;14)(p16;q32), but also amp(1q21).

Monoclonal protein (M-protein) is produced by a malignant clone of plasma cells. Detected in serum and/or urine, this typically indicates multiple myeloma (MM) or other monoclonal gammopathy (MG). In a majority of MM cases, with the production of intact monoclonal immunoglobulin (Ig), malignant plasmocytes and/or B lymphocytes often produce excessive amounts of free light chains (FLCs). Excessive synthesis of FLCs lowers the ability of renal proximal tubules to re-absorb FLCs, which results in abnormally high levels of FLCs in the urine (Bence Jones protein, BJP). In laboratory practice, there are tests available for the quantitative measurement of only FLCs κ and λ or for total light chains (TLCs). These tests measure both free forms and bound in the (Ig) molecules forms as light chains that are evident in the serum and in urine. The purpose of this study was to evaluate the FLCs and TLCs approaches in screening serum and urine samples of patients with MM, doing so in comparison to the results of immunofixation (IFE) assessment. A second purpose was to assess the suitability of the collected material for obtaining the most reliable results. The results of serum FLCs (sFLCs) assays suggest that this approach is of the highest reliability and diagnostic usefulness in the detection of MG with excess production of FLCs, in comparison to other available tests. In our work, when κ band light chains were detected in serum IFE (sIFE), 91% patients had their FLCs concentrations beyond the reference range, whereas 89% patients had increased λ FLCs when λ band light chains were detected in sIFE. We also found abnormal sFLC κ/λ ratios in 86.4% and 88.9% of all subject patients who had κ or λ band light chains detected in their sIFE, respectively.

Monoclonal gammapathies are a group of diseases characterized by proliferation of plasma clone cells that produce a certain type of homogenic immunoglobulin containing heavy chains of a, g, m, d, e class aside a type of light k or l chains. Standard methods applied to detect and identify the type of monoclonal protein in patients suspected of monoclonal gammapathy include serum electrophoresis and immunofixation. Quantitative analysis of free light chains (FLCs) by nephelometry has become more popular recently. The purpose of the study was to compare the results and assess the compatibility of free light chains measurements obtained by nephelometry and standard immunofixation. In addition to that, we tried to evaluate the usefulness of serum FLC analysis in the detection of monoclonal protein. The investigation was carried out in the group of 92 patients with suspected monoclonal gammapathy. In most cases concentrations of FLCs are increased depending on the type of light chain determined by immunofixation, however normal values of FLCs and normal kappa/lambda ratio do not exclude the presence of monoclonal protein. The analysis of FLC is most useful to identify patients suspected of light chain disease. Immunofixation is more sensitive method to detect gammapathies with complete monoclonal protein in comparison to quantitative FLC analysis.

Determination of FLCs in the blood serum has been useful to diagnose patients with monoclonal gammapathies. Besides, the test has been widely used to assess response to treatment and detect progressive conditions. In the course of gammapathy monoclonal light chains constitute homogenic population of chains made of kappa and lambda light immunoglobulins produced by malignant plasmocytes and/or B lymphocytes. Quantitative analysis of FLC by nephelometry and turbidimetry uses specific antibodies which recognize antigenic determiners of light chains. The purpose of our investigation was to compare nephelometric and turbidimetric methods applied in FLC determinations. Comparative determinations were done in the group of 64 patients suspected of monoclonal gammapathy: 30 females (mean age 66yrs) and 34 males (mean age 64yrs). The analysis of results let conclude that nephelometric and turbidimetric techniques applied to determine kappa and lambda free light chains have comparable diagnostic value.

Among hematological malignancies, the expression profile of programmed cell death-1 (PD-1) and its ligands in multiple myeloma (MM) is still debated by numerous research groups. In current study, we characterized the expression of PD-1 and its ligands both on RNA and protein levels in MM patients. We have also attempted to analyze whether daratumumab therapy might overcome CD38-mediated immunosuppression that inhibits in particular CD8+ T-cell function.Patients and Methods: This study included 149 newly diagnosed MM patients and 15 relapsed/refractory MM patients before and after daratumumab treatment. The mRNA levels of PDCD1, PDCD1LG1, PDCD1LG2 and their splicing variants was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Flow cytometry was used to characterize the surface expression of PD-1 and its ligands on plasma cells, B and T cells. The surface expression of PD-1 on T cells was assessed by flow cytometry before and after daratumumab treatment. Results:The mRNA expression of PDCD1LG1, PDCD1LG2 and their splicing variants were higher in plasma cells as compared to bone marrow mononuclear cells (BMMCs). Our results show that the percentage of plasma cells expressing PD-L1 was significantly higher than plasma cells expressing PD-L2 (p<0.0001) in bone marrow (BM) of MM patients. There was no significant difference between the percentage of plasma cells expressing PD-1 and B cells expressing PD-1 in BM of MM patients (11.19% vs 8.91%). We also found that the percentage of CD8+PD-1+ T cells was significantly higher than CD4+PD-1+T cells in BM (p<0.0001) of MM patients. Here, we observed no change in PD-1 expression on CD4+ and CD8+ T cells after the daratumumab treatment. Conclusion:The PD-1 and its ligands might represent an interesting target for MM immunotherapy, as one would target both malignant plasma cells as well as the immune cells that play a key role in tumor escape mechanisms.