PB2109 NICHEFORMING STRUCTURES OF BONE MARROW OF PATIENTS WITH MULTIPLE MYELOMA BEFORE AND AFTER AUTOHSCT

Abstract

Background: Autologous transplantation of hematopoietic stem cells (AutoHSCT) is one of the most effective methods of treatment in patients with MM, which can significantly reduce the volume of cells of the pathological clone and improve the quality of the response. However, there remain groups of patients with ineffective AutoHSCT: patients with unsuccessful mobilization and with early relapse after AutoHSCT. AutoHSCT success depends on many factors, including the state of the niche of HSC, which has been subjected to toxic effects of aggressive treatment and damaged by the underlying disease. Aims: To investigate the morphological characteristics of the main stromal components of the niche HSC and cultural characteristics of MSC patients with multiple myeloma (MM) before and after treatment, including AutoHSCT. Methods 32 trepanobiopsy of bone marrow from patients diagnosed with MM the ages of 48 and 68 (median age 56) before and after AutoHSCT were used in the study. The study applied histological, immunohistochemical and cultural methods. 20 patients diagnosed with primary MM included in the study. 12 patients diagnosed with progressive MM: inefficient mobilization of HSC was noted for 5 patients and early relapse for seven. Results: Changes of stromal microenvironment of bone marrow (BM) showed of all patients with MM: increased microvascular density and the number of endosteal stromal cells, strengthening of reticulin fiber in subendosteal and perivascular spaces. Increased angiogenesis correlates with the number of plasma cells in the myelogram (r = 0.58; p < 0.05) and with the type of infiltration of BM (r = 0.85; P < 0,05), as well as with osteodestructive changes in the patient's history (r = 0.65; p < 0.05). Shown significant changes in cultures of mesenchymal stromal cells (MSC), both before and after therapy, including AutoHSCT. In cultural studies of MSC BM MM patients compared to healthy donors showed a decrease in the speed of proliferation (2.4 times on average), a decrease in the total time of passionation from 7 to 5 passages. A marked increase expression of markers associated with myofibroblastic phenotype and aging (smooth-muscle actin, β-galactosidase) - 45-80% of cells in the culture were positively stained with these markers. In MSC cultures of patients after AutoHSCT β-galactosidase were synthesized weaker than before treatment, but nevertheless higher than in the control group. MSCS of healthy donors BM of the enzyme is almost not synthesized. Fibrils smooth-muscle actin was detected in MSCS to AutoHSCT, after AutoHSCT was practically absent. Summary/Conclusion: Thus, the cultures of patients with MSC and BM nicheforming elements of patients with MM possess the features of tumor-associated microenvironment, despite the treatment of the underlying disease.