Aim. To evaluate the concentration of immunoglobulin free light chains (FLC) in comparison with that of intact measurable paraproteins (PIg) in patients with relapsed/resistant multiple myeloma (RR MM) undergoing treatment with bortezomib.

Materials and methods. A retrospective study included 15 patients with RR MM with intact measurable PIg. Following 6 cycles of bortezomib treatment, an evaluation of the treatment efficacy was performed using standard criteria and by analysing serum FLC of immunoglobulins (sFLC).

Results. A partial response (PR) and small response was achieved in 4 and 5 patients, respectively. The stabilization of the disease was observed in 6 patients. No cases of complete response (CR) or stringent complete response (SCR) were recorded. On the basis of the data on the concentration of sFLC after treatment, all patients were divided into 2 groups: those with an abnormal (clonal) and normal κ/λ ratio. In 11 patients with a response lower than PR, sFLC κ/λ ratio was of a clonal nature, which corresponded to changes in the concentrations of intact PIg during treatment. In 4 cases with PR, the residual tumour was determined by the presence of intact PIg within the 32–45 % range under, however, a normal sFLC κ/λ ratio.

Conclusion. Treatment with bortezomib affects all processes in MM with intact PIg, such as synthesis of FLC by tumour plasma cells, a decrease in the amount of circulating sFLC in blood and in the concentration of intact PIg. Normalization of sFLC κ/λ ratio under the achievement of PR could be considered as a prognostic factor in a favourable clinical outcome.

Aim. To determine the dynamics of cryoprecipitate production in Russian blood service institutions in comparison with such institutions in other countries.

Materials and methods. Reports provided by Russian blood service institutions during the 1997–2017 period were analysed, along with European standards for blood collection and transfusion.

Results. Over the 1997–2004 period, the number of cryoprecipitate units issued annually ranged from 263,897 (2000) to 297,890 (2002) units. Over the subsequent 8 years, the number of annually released cryoprecipitate decreased to 23,663 units, having reached a historical minimum in 2012. From 2012 to 2017, the number of annually issued cryoprecipitate units increased by 80.0 %, reaching the amount of 42,589 units. Reasons for such a wavelike dynamics in cryoprecipitate production in Russia have been determined. In addition, directions for expanding the use of this product in the correction of hypofibrinogenemia have been identified.

Conclusion. Cryoprecipitate should be re-introduced into the practice of clinical transfusiology. To this end, national clinical guidelines for cryoprecipitate application should be developed.

Aim. To evaluate the efficacy of DSP30 in combination with IL2 in cultivating blood cells/bone marrow/lymph nodes in chronic lymphocytic leukemia (CLL) patients to detect clonal abnormalities.

Materials and methods. The study included 50 patients with CLL, all of whom underwent both chromosome banding analysis (CBA) (46 patients with DSP30+IL2 and LPS+TPA; 4 patients with only DSP30+IL2) and FISH with DNA probes to detect trisomy 12 and deletions of 13q14, 11q22 and 17p13.

Results. Under cell cultivation with DSP30+IL2 and LPS+TPA, CBA was successfully performed in 41 (82 %) and 38 (83 %) patients. Chromosome aberrations were observed in 36 (72 %) and 15 (33%) cases, while a complex karyotype was detected in 13 (26%) and 5 (11%) cases, respectively. A significant difference was found between the number of metaphases with chromosomal abnormalities obtained by cultivation with DSP30+IL2 and LPS+TPA (V = 490.5, p < 0.05). CBA revealed balanced translocations in 6 patients, with the involvement of the IgH/14q324 locus being confirmed in 4 cases. Unbalanced translocations and various combinations of translocations were detected in 11 and 6 patients, respectively. In 5 cases, according to CBA, the results of 13q14, 11q22, 17p13 deletions identified by FISH were accompanied by balanced or unbalanced translocations in these loci. Unbalanced t(12;16)(q14;q23) — a case of partial trisomy — was detected only by CBA with DSP30+IL2.

Conclusions. An abnormal karyotype was detected in CLL patients twice as more frequently under cultivation with DSP30+IL2 compared to LPS+TPA. CBA is an important method allowing the structure of chromosomal abnormalities to be specified and translocations to be identified. As a result, patients running the highest risk of CLL — those with a complex karyotype — can be singled out for selecting an optimal strategy of their management.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a standard treatment for many patients with hematological malignancies. Complications of allo-HSCT are frequently associated either with a relapse of the underlying disease or a graft failure. Second transplantation can be offered to selected patients and is seen as the only curative option. In this paper, we report the experience of managing 24 such patients, all of whom underwent a second allo-HSCT.

Patients and methods. The research involved 24 patients (12 males/12 females) suffering from acute myeloid leukemia (AML, n = 14), acute lymphoblastic leukemia (ALL, n = 4), myeloproliferative disease (MPD, n = 3) and myelodysplastic syndrome (MDS, n = 3). The patients’ age ranged from 18 to 56 years, with the median age being 32 years. All the patients underwent a second allo-HSCT due to the disease relapse (n = 11) or graft failure (n = 13). 12 patients underwent a second allo-HSCT within the period of less than 6 months after the first allo-HSCT.

Results. Following the second allo-HSCT, engraftment occurred in 18/24 (75 %) patients, while 3 patients demonstrated graft failure and 3 — disease progression. Out of 18 patients having engrafted, 9 (50%) died during the first 100 days after allo-HSCT as a result of severe infections or visceral toxicity. 3 more lethal outcomes were recorded in later periods due to the disease progression. The overall mortality rate after the second allo-HSCT equalled 61.5 %. The median overall survival (OS) and disease-free survival (DFS) rates were 13.5 months and 10.59 months, respectively. Three-year OS and DFS were 38.5 % and 27.6 % respectively. Significant differences in terms of OS were detected for patients with a longer interval (>6 months) between the first and second allo-HSCT. The change of a donor was not associated with a better clinical outcome.

Background. Gaucher disease is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme glucocerebrosidase, which is required for the degradation of glycosphingolipids. Skeletal involvement is one of the main manifestations of the disease and is present in 70–100 % of patients. However, the rarity of Gaucher disease and non-specific and heterogeneous nature of its symptoms and radiological signs may impede consideration of this disease in the differential diagnosis.

Aim. To describe the radiological signs of bone involvement in type I Gaucher disease and assess the role of MRI in the evaluation of the severity of the disease in newly diagnosed patients.

Materials and methods. X-ray and MRI data of 86 treatment-naïve Gaucher patients were included in the retrospective analysis. Bone marrow involvement, as well as bone and joint pathological changes, were evaluated.

Results. Radiological signs of bone involvement in Gaucher patients were described and classified into 2 groups, i.e. reversible and irreversible. Such a classification is important in terms of the assessment of the overall disease severity. MRI has proven to be a sensitive method for detection and evaluation of the reversible bone changes in Gaucher patients.

Conclusion. Although radiological manifestations of bone involvement in Gaucher patients are typical, they may significantly vary and be present in various combinations. MRI is the gold standard for the assessment of bone marrow changes in patients with Gaucher disease.

Background. Von Willebrand disease is a hereditary malfunction of the blood coagulation system caused by waveform quantitative and/or qualitative deficiency of von Willebrand factor (vWF).

Aim. To evaluate the frequency of occurrence of FVLeiden and FII G20210A mutations in female patients with von Willebrand type 1 disease.

Materials and methods. 136 women aged from 18 to 45 years (mean 31.7 ± 0.5 years) were enrolled in a study conducted during the January 2011 — December 2017 period. Questionnaire was used to reveal hemorrhagic diathesis. Inclusion criteria were as follows: no less than 3 positive responses to questions 1–7, or 2 positive responses to questions 1–7 plus no less than 100 points of the evaluated menstrual blood loss. An independent inclusion criterion was 180 points or more in the question concerning menstrual blood loss. A mandatory inclusion criterion was the confirmation of absence of thromboembolic events in a proband and first line relatives. The study included assessment of such parameters as ristocetin-cofactor activity of von Willebrand factor (vWF:RCo), von Willebrand factor antigen (vWF:Ag), factor VIII (FVIII:C), platelet aggregation induced with ADP, ristomycin, collagen, as well as molecular-genetic assay of factor V (FVLeiden) and gene (FII G20210A) polymorphism using allele-specific polymerase chain reaction.

Results. No mutations of FVLeiden and FII G20210A were revealed in 102 women with von Willebrand disease type 1. Heterozygous mutation of FVLeiden was found in 12 (8.8 %) subjects with von Willebrand disease type 1 (vWF:RCo from 27 to 47 % (mean 37.3 ± 0.8 %), vWF:Ag from 25 to 46 % (mean 37.5 ± 0.8 %), FVIII:C from 29 to 49 % (mean 44.1 ± 0.5 %). Homozygous mutation of FVLeiden was identified in 3 (2.2%) women with von Willebrand disease type 1, with vWF:RCo being 40, 43 and 45 %, vWF:Ag — 39, 44 and 42 %, FVIII:C — 47, 45 and 48 %, respectively. Heterozygous mutation FII G20210A was detected in 19 (13.9 %) subjects with von Willebrand disease type 1 (vWF:RCo from 36 to 49 % (mean 43.0 ± 0.4 %), vWF:Ag from 32 to 46 % (mean 42.2 ± 0.6 %), FVIII:C from 30 to 49 % (mean 45.1 ± 0.4 %).

Conclusion. By means of diminishing the coagulation potential of the blood coagulation system, a decrease in the activity of VIII and von Willebrand factors may compensate possible negative effects associated with FVLeiden and FII G20210A gene mutations in female patients with von Willebrand type 1 disease.

Background. Immunological and infectious safety of blood components is considered to be a key condition for high-quality transfusion therapy. The progress of blood filtration methods contributes to the development of methods for the validation of residual leukocyte control in blood products.

The aim of the study was to compare the efficiency of flow cytometer with hematology analyzer for counting residual leukocytes in blood products

Methods. In this study, we compared the efficiency of two analytical instruments for counting residual leukocytes in 191 blood plasma samples: a flow cytometer (Navios Beckman Coulter) with a LeukoSure commercial reagent kit and a Sysmex XT4000i hematology analyzer.

Results. All the samples under investigation met technical regulation requirements. Most of the samples were characterized by a significantly low amount of residual leukocytes, which fact presented a particular scientific interest. The use of a Navios Beckman Coulter flow cytometer and a commercial reagent kit allowed us to detect 15 or lower cells per μL in 83 % of the samples. The use of a Sysmex XT- 4000i automatic hematology analyzer for the calculation of residual white blood cells in this range proved to be limited due to the sensitivity of the device and the absence of certified reference materials with a low white blood cell count.

Conclusion. Our results show that a Navios Beckman Coulter flow cytometer with a commercial reagent kit is suitable for measuring residual leukocytes in blood plasma. This instrument is most appropriate for samples with a minimum number of cells. A significant variability of the amount of residual white blood cells in blood plasma confirms the importance of inspecting the content of leukocytes in all blood components.

Aim. To present a technique for obtaining fibrinogen concentrate purified from ballast proteins, which can be used in hemostatic drug production.

Materials and methods. The proposed method is based on isolating fibrinogen from a cryoprecipitate solution by its precipitation with a polyethylene glycol solution followed by virus inactivation by a solvent/detergent. Purification from viral inactivation products and ballast proteins is performed by a two-step processing of the obtained fibrinogen concentrate with glycine solution.

Results. The developed laboratory method for isolating fibrinogen has been optimized in terms of main parameters and scaled in pilot production.

Conclusion. The presented laboratory technique for fibrinogen extraction is characterized by a high yield of the target product, thus being suitable for the production of hemostatic drugs.

Background. The regimens of therapy with bortezomib have significantly improved the survival among patients with multiple myeloma (MM). However, the development of peripheral polyneuropathy (PP) resulting from treatment using proteasome inhibitors is still an undesirable event. Risk factors for PP in MM patients include old age, previous neuropathy and use of neurotoxic drugs. Recent studies have established the presence of a genetic component in the mechanism of developing bortezomib-induced neurotoxicity. However, there are conflicting opinions on the role of genetic characteristics in predicting the risk of treatment-induced neuropathy development.

Aim. To identify the risk group of bortezomib-induced PP based on the analysis of gene polymorphism of the immune response in patients with newly-diagnosed MM.

Materials and methods. A study of the association of 20 polymorphic loci of 14 immune response genes in 46 MM patients was conducted using a candidate gene identification approach. All the patietns were receiving VCD therapy with bortezomib.

Results. The distribution of single nucleotide polymorphisms was compared in groups of patients with the presence and absence of PP. It is found that homozygous carriers of the wild type allele of the genes TLR6 (Ser249Pro) (p = 0.006), IL1β (G-1473C) (p = 0.04), IL4 (C-589T) (p = 0.04), as well as haplotype carriers with the mutant allele of the gene IL10 (G-1082A) (p = 0.04) and with the wild type allele gene IL2 (T-330G) (p = 0.01) were significantly more frequent among PP patients.

Сonclusion. Our results have confirmed the contribution of the genetic component to the risk of developing bortezomibinduced neuropathy. These findings can be used for individualization of therapeutic approaches to the treatment of MM patients.

In this paper, we present a literature review with the purpose of elucidating the pleiotropic effects of oral anticoagulants. The literature search was performed using the PubMed and SCOPUS databases. Pleiotropic effects of direct anticoagulants are determined by the interaction of Xa and thrombin IIa factors with PAR-1 and PAR-2 receptors. The focus of this review is the connection between oral anticoagulants and their effects on atherosclerosis, angiogenesis, inflammation, cardiac remodelling, oncogenesis and glomerular diseases. Direct anticoagulants exhibit an anti-atherosclerotic effect manifested in a decreased progression and destabilization of atherosclerotic lesions. This effect is confirmed by a decreased binding activity of DNA with NF-kB and AP-1 transcription factors and reduced levels of some mediators. Such effects of new oral anticoagulants also relate to the processes of cardiac remodelling. FXa inhibitors contribute to the prevention of cardiac remodelling by reducing the processes of inflammation and fibrosis, which are associated with a decrease in the expression of PAR receptors in the heart. A number of studies also demonstrate an anti-inflammatory effect of oral anticoagulants, which is confirmed by reduced expression of mRNA inflammatory cytokines under the influence of direct anticoagulants and the production of IL-6 under the influence of warfarin. FXa inhibitors are shown to increase the expression of vascular growth factors, stimulate the migration of еndothelial рrogenitor сells and improve their function, thus manifesting their angiogenic pleiotropic effect. In addition, warfarin has an impact both on angiogenesis by means of reducing the activation of Axl tyrosine kinases and on glomerular pathologies by means of affecting the proliferation of mesangial cells through the Gas6/Axl pathway. The antitumour activity of warfarin is associated with inhibition of Gas6-mediated activation of Axl on tumour cells. Further investigations are required to fully understand the effect of oral anticoagulants on haemostasis.