Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of auto-HSCT efficacy. Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied. Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with auto-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (р = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (–174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (р = 0.038). Conclusion. The carrier status of IL6 (–174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.