PB2375 THE DYNAMICS OF THE CONTENT OF HEMATOPOIETIC CYTOKINES IN BLOOD SERUM OF PATIENTS WITH MULTIPLE MYELOMA WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: T. Glazanova, O. Rozanova, A. Zhernyakova, L. Bubnova, A. Chechetkin, S. Bessmeltsev, S. Gritsaev
Journal: HemaSphere (2019)

Background: Autologous hematopoietic stem cell transplantation (autoHSCT) is an integral part of the treatment of patients with multiple myeloma (MM). AutoHSCT increases the frequency and duration of relapse-free and, according to some data, overall survival. However, high-dose therapy negativety affects the vital organs, reduces somatic status and quality of life (QoL). Along with the regulation of inflammatory processes, cytokines are an integral part of normal hematopoiesis and affect all of its stages, inducing and regulating cell proliferation, differentiation and apoptosis. They can be rated as hematopoietic factors (e.g. IL-1 b) and their suppressants (e.g. TNFа); IL-6 has pleiotropic action with multidirectional effect on hematopoietic cells, and IL-17 regulates pro-inflammatory cytokine production and induces the production of a variety of pro-inflammatory cytokines (e.g. TNFα, IL-6), while IL-4 and IL-10 have anti-inflammatory effect. Aims: To investigate the dynamics of various cytokines in the process of hemopoiesis recovery in patients with MM after auto HSCT, and, subsequently, to identify the association of dynamic changes in their level with indicators of QoL, the frequency of infectious complications and the time of engraftment. Methods: A total of 32 patients with MM who received autoHSCT were examined, including 6 patients with repeated autoHSCT. The regimen of conditioning (RC) comprised the administration of melphalan 200 mg/m2 or a combination of thiotepa with melphalan. Using the standard ELISA method, we have studied the serum levels of the following cytokines: IL-1b, TNFa, IL-4, IL-6, IL-10 and IL-17A. Evaluations were performed prior to the start of the conditioning regimen and on Days 0, +1, +7, +30, and +100 after autoHSCT. Results: It is worth noting that changes in the levels of the studied cytokines were multidirectional, from minor (for IL-1 b and IL-4) to statistically significant. Thus, the content of TNFa on Day 0 was significantly reduced (by 2.6-fold) compared with the baseline (before the RC), and this decrease persisted by Day +1; later (by Day +100), this indicator was restored to baseline values. Significant, but oppositely directed changes were observed for the content of IL-6: a significant increase (8.3-fold) on Day +7, followed by a decrease by Day +30, however, this indicator remained 1.5-fold higher than the “before RC” point. The most stable changes were observed for IL-10: the level of this anti-inflammatory cytokine was significantly increased compared with the baseline at all time points, and the degree of its increase ranged from 1.6-fold to 3.01-fold. At the same time, the level of pro-inflammatory IL-17A was significantly reduced on day +7 (2.1-fold). Summary/Conclusion: The results indicate a multidirectional dynamic change in the cytokine level in patients with MM receiving autoHSCT, which probably reflects the intensity of the immune system to preserve the body homeostasis. The number of examined patients is not enough to identify the association of cytokine levels with the frequency of infectious complications, the duration of postcytostatic cytopenia and QOL, and thus requires further accumulation of data.