AM of the p15NK4b and SOX7 genes and Wnt signaling pathway antagonists is detected in the majority of patients with AML, which allows hypomethylating agents to be recommended for the treatment of patients who cannot use intensive cytostatic therapy for different reasons. The detection of a large number of genes with the aberrant methylation status in most AML patients with myelodysplasia or a complex karyotype serves as the basis for initiating trials to evaluate the efficiency of a combination of 5-azacytidine and cytostatics.
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 au-to-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 au-to-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (p = 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 (p = 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.
Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT). Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38-66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 <sup>x</sup> 10<sup>6</sup>/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher's exact test with measurements of odds ratio (OR) and р-value was used. Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B -31C (OR 2.7; p = 0.029). The proportion of heterozygous -174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; p = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 x 10<sup>6</sup>/kg the proportion of those with IL10 -592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; p = 0.091). Conclusion. The present study confirms the relationship of -31C/T polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of -174G/C polymorphism in IL6 gene and -592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.
equal to 3) of 53.5%. The mean creatinine clearance value was 118.48 ml/min and the mean follow-up of these patients was 13.57 months. Results: : It has not been reported any case of Stroke, Systemic Embolism, or Major Bleeding (according to the criteria of the ISTH) during the follow-up time of the patients treated, both in the main group and in the subpopulation of patients with creatinine clearance above 95 ml/min. Only 3% of patients (17) had complications with Edoxaban, of which 12 had discontinued treatment for this cause. No case of severe or clinically relevant major bleeding has been reported according to the ISTH criteria. During the time of follow-up, twelve cases of death occurred from their base disease or from other causes, but in no case related to Edoxaban. Summary/Conclusion: This is a good sample of 552 patients and more than with a mean of 13 months of follow-up. In the analyzed subpopulation of patients with creatinine clearance greater than 95 ml/min, the good results of Edoxaban are confirmed since they have not presented any stroke recurrence or systemic embolism or major or clinically relevant hemorrhage according to the ISTH criteria. Due to the sample of 127 patients, more studies will be needed to confirm this assertion.
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