Background. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an indispensable treatment stage in patients with newly diagnosed multiple myeloma (MM) who are, based on age and health status, eligible for high-dose chemotherapy with subsequent auto-HSCT. However, the issue of double (tandem) auto-HSCT feasibility remains unresolved. Aim. To compare overall survival (OS) and progression-free survival (PFS) in MM patients after single and double (tandem) auto-HSCTs in clinical practice. Materials & Methods. Retrospective analysis enrolled 83 MM patients divided into two groups: with single (n = 41) and double (n = 42) auto-HSCTs. Median age in groups 1 and 2 was 58 years (range 42-68) and 54 years (range 40-65), respectively. In these groups there were 16 (39 %) and 11 (26.2 %) patients > 60 years old. The reference point of survival curve was the date of first (in group 1) and 2nd (in group 2) auto-HSCTs. In PFS assessment, completed event was the date of disease progression or relapse detection, including the biochemical one in case of specific therapy onset. Results. Total number of patients with > very good partial response before receiving auto-HSCT in group 1 was 23 (56.1 %), and in group 2 before receiving 2nd auto-HSCT it was 30 (71.4 %). Mel200 conditioning was administered to 53.7 % of patients in group 1. In group 2 this conditioning regimen was a priority in performing first auto-HSCT (83.3 % of patients) and was more rarely used in case of repeated transplantation (40.5 %). With median follow-up of 11 and 40.5 months in groups 1 and 2 no significant differences were identified either in median PFS (21 and 40 months; p = 0.154) or in median OS (not reached in both groups; p = 0.882). No differences between groups with respect to the time before relapse/progression or early relapse rate were observed. Conclusion. Repeated auto-HSCT showed no additional antitumor effect. It can be accounted for by the lack of data on chromosome aberrations at the disease onset in most patients and by a small number of patients in the groups. Nevertheless, it was decided to limit the number of tandem auto-HSCTs and to perform 2nd transplantation mostly in case of late relapse/progression. New studies were initiated which will focus on the search of predictors associated with survival improvement in MM patients while performing double (tandem) auto-HSCTs.
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.
Background:Background: One of the ways to increase the intensity of conditioning regimen is the adding of additional drug to melphalan. Supposed that combination of drugs has more potential to reduce the myeloma cells content, which translates into improved progressive-free survival. On the other hand, the development of prolonged cytopenia with extended hospital stay is not exclude. Aims:Aims: Comparative assessment of graft engraftment time in patients with multiple myeloma (MM) after autologous stem cell transplantation (AutoSCT) using four conditioning regimens: Mel200, Mel140, melphalan with thiotepa (Mel/Thio) and melphalan with carfilzomib (Mel/Carfil). Methods: Methods:The data of 53 patients with MM analyzed. The number of patients who received Mel200, Mel140, Mel/Tio and Mel/Carfil regimens prior to infusion of thawed cell suspension was 24, 13, 10 and 6, respectively. Eleven AutoSCT (20.8%) were the second ones. The conditioning regimen with reduced dose of melphalan (Mel140) was prescribed predominantly for the second transplantation: 6 (46.2%) vs 3 (12.5%) for the first AutoSCT; p=0.022. In the posttransplant period. granulocyte colony-stimulating factor (G-SCF) was received by 20 (83.3%), 12 (92.3%), 8 (80.0%) and 5 (83.3%) patients in the respective groups. Results:Results: The median achievement by the absolute number of neutrophils at the level 0.5x10/9/L and more in the groups was 10 (6-15), 13 (9-19), 10 (9-11) and 14 (10-18) days, respectively. The difference in enraftment time was significant between the Mel/Thio and Mel/Carfil groups; p=0.012. There were no difference in the number of patients with episodes of febrile neutropenia: 6 (25.0%), 2 (15.4%), 3 (30.0%) and 1 (16.7%), respectively. Three (12.5%) patients with Mel200 regimen and 1 (10.0%) patient with Mel/Thio regimen did not have thrombocytopenia below 20x10/9/L. In other patients, the median of reaching platelet level 20x10/9/L and more did not differ: 14 (17-19), 14 (9-19), 13 (10-15) and 15 (12-16) days, respectively. The median number of infused platelets doses did not differ either: 2.5 (1-5), 3 (2-6), 2.5 (1-4) and 2 (1-2), respectively. The length of stay of patients in the hospital from the day of infusion of thawed cell suspension to discharge was as follow: 17.5 (12-21), 19 (14-26), 16 (15-20) and 18 (14-20) days, respectively, differences no.
The effectiveness of multiple myeloma (MM) patients’ treatment is dependent in particular on the depth of response after autologous stem cell transplantation (аutoHSCT). The importance of predictors associated with the quality of response after аutoHSCT is due to the possibility of changing the intensity of some stage of transplantation. The aim of the study was to determine the incidence of cases without the improvement of response depth after autoHSCT and to evaluate the distribution of genotype of a number of genes and status of hemopoietic niche cells as a possible predictor of аutoHSCT effectiveness in MM patients. Retrospective analysis of 84 MM patient’s data was carried out. Total number of transplants performed was 112 including 84 first and 28 second transplants. The response was determined according to IWG criteria. Status of hemopoietic niche cells was evaluated by histological, immunohistochemistry and morphometric methods. Improvment of the response depth after the first аutoHSCT was recorded in 29 (54.7%) patients. Similar events were higher in the patients with previous VGPR: 57.9% vs 18.2% in patients with PR; p=0.005. There was no difference in other clinical and hematologic parameters between the groups. After the second аutoHSCT the variant of response did not change in 4 out of 6 patients. The deepening of response occurred significantly more often in cases with more cells localized on endost; p=0.038. The results of bone marrow trepanobiopsy can be considered as predictors of a possible improvement in the quality of response or lack thereof in patients with MM after performing аutoHSCT.
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