PB2152 THE ROLE OF THE BONE MARROW MICROENVIRONMENT AND CYTOKINES IN THE PROGRESSION OF MONOCLONAL GAMMAPATHY AND MULTIPLE MYELOMA IN PATIENTS OF THE GOMEL REGION OF BELARUS
Authors: Kozich Z. , Zinovkin D. , Zhandarov M. , Pugacheva Z. , Korotaeva L. , Smirnova L. 
Published: June 2019

Background:

Multiple myeloma (MM) is an incurable tumor of hematopoietic tissue. In its development, it goes through a stage of monoclonal gammopathy (MGUS) or smoldering myeloma, when a tumor clone is born. With monoclonal gammopathy, the percentage of clonal plasma cells is less than 10%, therefore, during cytological examination of the bone marrow, it is not always possible to determine any specific differences between myeloma cells and normal plasma, therefore, an immunohistochemical study of the bone marrow and a combination of various biochemical markers help in this situation.

Aims:

Assess the role of the bone marrow microenvironment and the prognostic significance of some cytokines in the progression of diseases in monoclonal gammopathy and multiple myeloma.

Methods

The study was carried out on samples of whole venous blood, aspirate and bone marrow biopsy material of 30 patients (12 patients with monoclonal gammapathy and 18 patients with multiple myeloma). The median age was 64 years for MGUS and 65 years for MM.

All patients have undergone blood tests for cytokines, immunoglobulins, kappa and lambda light chains, cytological, immunophenotypic and immunohistochemical studies of the bone marrow. Results were evaluated at the time of diagnosis. The number of clonal plasma cells in the bone marrow in patients with MGUS averaged 3.5% (0.6‐11.2%), in patients with MM 42.2% (12.2‐72.6%). According to immunochemical variants, MM and MGUS are represented by secretion of IgG, IgA, IgM, secretion of kappa and lambda light chains. The level of CD138 positive cells, kappa, lambda chains, the myelokariocyte count, the presence of bone marrow fibrosis were assessed immunohistochemically.

Results:

When comparing immunohistochemical data for MGUS and MM at the time of diagnosis, a significant excess of the level of CD138 positive cells was found with a significant excess of the count of kappa and lambda light chains in blood serum and bone marrow in patients with MM. In patients with MGUS, the CD138 positive cell count during immunohistochemistry was significantly higher than in the bone marrow immunophenotypic study (p <0.0001) and was accompanied by significant kappa or lambda chains expression in the peripheral blood and bone marrow, which may indicate a possible early generalization of the process and MGUS progression in MM. In all patients with MGUS and expressed expression of CD138 positive cells, the immunohistochemical study showed a significant excess of TNF (p <0.001; r = 0.693), interleukin‐6, interleukin‐8, and were accompanied by lambda light chain secretion (p <0.001; r = 0.698), which suggests the production of cytokines by tumor plasma cells. During follow‐up (6 months) in two MGUS patients with these characteristics, the disease transformed into MM and in one patient with IgM secretion into Waldenstrom macroglobulinemia. Fibrotic changes in the bone marrow during MGUS were combined with lambda light chain production, increased production of interleukin‐6 and interleukin‐8, a decrease in the number of megakaryocytes in the bone marrow (p <0.001; r = 0.698), which may indicate a bone marrow reassociation associated with possible tumor progression.

Summary/Conclusion:

When analyzing the results of bone marrow immunohistochemical indicators, blood cytokines in our study revealed an increase in the number of CD138 positive cells and a significant excess of cytokines in the producing tumor cells in MGUS, the appearance of fibotic changes and a decrease in the number of myelokariocyte, which can be a significant biomarker of the risk of progression in monoclonal gammapathy.