Currently, there has been a marked increase in the number of opportunities for relapsed and refractory multiple myeloma treatment due to emergence of new target drugs. These include pomalidomide, a 3 rd generation immunomodulator capable of treating double refractory multiple myeloma (to lenalidomide and bortezomib). Efficacy and safety of pomalidomide combined with low doses of dexamethasone have been established in MM-003 and STRATUS trials. The summary presents the data on opportunities to further enhance the efficacy of pomalidomide combined with other antitumor drugs in patients with relapsed and refractory multiple myeloma who previously received 4–5 lines of therapy. It has been shown that triplets based on pomalidomide and dexamethasone combined with cyclophosphamide, bendamustine, daratumumab, carfilzomib, elotuzumab are highly effective in double refractory multiple myeloma patients. A combination of pomalidomide with proteasome inhibitors is a promising treatment provided that there is no refractoriness to bortezomib.

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM).
Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses.
Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted.
Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

Background. Children and adolescents undergoing treatment in the hospital for blood diseases are at risk of thrombotic complications. However, to date no major studies of the prevalence of thrombosis in this category of patients have been conducted in Russia.
The objective: to determine the incidence of symptomatic and asymptomatic deep vein thrombosis (DVT), as well as their distribution by gender and age in children with various blood disorders.
Materials and methods. Medical records of 1962 patients, aged from 0 to 17 years, were retrospectively analyzed. All DVT cases were confirmed by visualization methods. The presence of thrombosis clinical signs detected during physical examination, allowed identifying symptomatic DVT.
Results. DVT was diagnosed in 429 patients; the symptomatic (n = 110) and asymptomatic (n = 337) DVT were considered as two independent groups with cases of thrombosis. The highest incidence of thrombotic complications was found in children with acute lymphoblastic leukemia (ALL) – 30.77 %, non-Hodgkin’s lymphomas – 22.58 %, other malignant blood disorders – 18.75 %, myeloid leukemia – 15.63 %, Hodgkin’s lymphoma – 16.50 %, histiocytosis – 12.5 %, aplastic anemia – 7.94 %, other leukemia – 7.14 %. Symptomatic episodes were more common in patients with lymphomas, especially non-Hodgkin’s, and ALL, while asymptomatic DVT were more common among children with ALL.
Conclusion. The DVT prevalence in children with blood disorders exceeds 20 %, most of them are asymptomatic thrombosis, while symptomatic DVT are much less common. Patients receiving treatment for lymphomas and ALL have the highest number of venous thrombotic complications. Further research is needed to address the need for primary thrombotic prophylaxis in children with blood disorders.

Objective: to evaluate the genetic relatedness of extended-spectrum β-lactamase (ESBL) producing Escherichia coli isolated from the gut in patients with acute myeloid leukemia and lymphoma at admission and during chemotherapy cycles.
Materials and methods. The prospective study (2013–2014) included 73 patients (median age 39 years) with acute myeloid leukemia (n = 25) and lymphoma (n = 48). The follow-up period lasted for 96 days. ESBL-producing E. coli isolated from the gut were included in this study. ESBL-production was confirmed by phenotypic tests, blaCTX-M and blaTEM genes were detected by polymerase chain reaction, and genotyping was performed by ERIC (Enterobacterial Repetitive Intergenic Consensus) polymerase chain reaction.
Results. ESBL-producing E. coli were detected in 39 (53 %) of 73 patients: of them 12 (16 %) patients were colonized at admission and 27 (37 %) patients – during chemotherapy cycles. Gene blaCTX-M was detected in 67 % of E. coli, blaTEM – in 41 %, both genes – in 26 %. There was no genetically related ESBL-producing E. coli among 12 isolates detected at admission. Genetic relatedness was detected in 16 (59 %) of 27 isolates obtained during a hospital stay. Genetically related ESBL-producing E. coli were isolated from patients hospitalized in the same and different departments, these isolates were characterized by the presence of both identical and various determinants of resistance.
Conclusion. Our data demonstrated the possibility of patient-to-patient transmission of ESBL-producing E. coli isolated from the gut during a hospital stay.

We presented two cases of invasive aspergillosis (IA) in children with solid tumors, data of IA patients register, and a literature review. In the register of patients with IA (1997–2018), we found 57 patients with IA from 0 to 18 years. It was established that the number of patients with solid tumors was 15.7 %. Background diseases were: central nervous system tumors – 33.5 %, neuroblastoma – 33.5 %, osteosarcoma – 11.0 %, Wilms tumor – 11.0 %, hemangioblastoma – 11.0 %. Chemotherapy-induced neutropenia was reported in 100 % of IA cases in children and adolescents with solid tumors. The additional risk factors were treatment in intensive care unit – 22.2 %, high-dose chemotherapy with autologous hematopoietic stem cell transplantation – 22.2 %, concomitant bacterial infection – 33.0 %. Surgical intervention for the underlying disease was performed in 77.7 % of patients. The most common clinical site of IA was the lungs – 88.9 %. The predominant clinical sign was fever – 66.7 %, cough and respiratory failure were seen less frequently – 33.4 % and 33.4 %, respectively. The etiological agents of IA were Aspergillus fumigatus – 33.3 %, Aspergillus nidulans – 33.3 % and Aspergillus ustus – 33.3 %. 88.9 % of patients received antimycotic therapy, voriconazole predominantly – 66.7 %. Combination therapy was used in 33.3 % of patients. The overall 12-week survival in children and adolescents with IA in case of solid tumors was 77.8 %.

Objective: a comparative clinical and economic analysis of posaconazole (Noxafil) for invasive mycoses (IM) prevention in patients with severe neutropenia during treatment of acute myeloid leukemia or myelodysplastic syndrome in Russia.
Materials and methods. A model was constructed that takes into account the use of various mediactions: posaconazole, voriconazole and fluconazole. Cost estimation for IM prevention was carried out considering the direct medical costs of IM prevention, IM therapy, hospital stay, therapeutic and diagnostic procedures and monitoring in case of IM. “Cost–effectiveness” and “budget impact” analyzes were performed.
Results. Based on literature data, high efficacy and safety of posaconazole for IM prevention in patients with severe neutropenia during treatment of acute myeloid leukemia or myelodysplastic syndrome was shown.
Cost analysis of drugs showed the lowest total costs for IM prevention with posaconazole – 185,745.49 rubles, followed by fluconazole – 275,360.26 rubles, and voriconazole – 299,792.76 rubles. At the same time, in the structure of total costs, for posaconazole and voriconazole, the cost of IM prevention prevailed – 155,017.17 rubles and 156,393.92 rubles, respectively, whereas for fluconazole – the costs of IM treatment – 168,390.45 rubles. This is due to the significantly higher incidence of IM cases in fluconazole group compared with posaconazole and voriconazole.
The use of posaconazole also showed the best ratio of cost–effectiveness for one prevented case of infection and for one extended year of the patient’s life (191,490.20 rubles and 34,980.32, respectively). Due to lowest costs and best efficiency of posaconazole, the incremental cost– effectiveness ratio (ICER) was not calculated.
Thus, the use of posaconazole for IM prevention in acute myeloid leukemia patients can reduce the overall cost per patient by 114,047.27 rubles compared with voriconazole and by 89,614.76 rubles compared with fluconazole.
The sensitivity analysis for cost–effectiveness results demonstrated the stability of IM prevention model in acute myeloid leukemia patients to changes in the initial posaconazole price upwards to +61 %.
The model has the highest sensitivity to IM incidence with unsuccessful prevention.
“Budget impact” analysis of IM prevention in acute myeloid leukemia patients older than 13 years in Russia showed that an increase in the posaconazole proportion from 25 to 50 % with a decrease of voriconazole proportion from 25 to 15 % and fluconazole proportion from 50 to 35 % in government procurement will reduce budget costs by 48.1 million rubles.
The sensitivity analysis for “budget impact” results showed the greatest sensitivity to changes in the patient number and to increase of posaconazole proportion in procurement. Results were less sensitive to an increase of voriconazole and fluconazole proportion.
Conclusion. The results of the study showed that the use of posaconazole for the prevention of invasive mycoses in patients with severe neutropenia during treatment of acute myeloid leukemia and myelodysplastic syndrome is clinically effective and economically justified within the system of state preferential drug provision in the Russia.

Multiple myeloma originating from clonal proliferation of plasma cells in the bone marrow is one of the most prevalent hematological malignancies worldwide. The pathogenetic mechanisms of multiple myeloma are far from being elucidated. Nevertheless, it is known that the adipocytes as the prevalent cellular component of bone marrow microenvironment contribute significantly to multiple myeloma growth and progression. The review discloses the recent data on the interactions between bone marrow adipocytes and myeloma cells, hematopoietic stem cells, hematopoietic progenitor cells, mesenchimal stem cells, osteoblasts, osteoclasts, endothelial cells, and cells of immune system. Also, the review places special emphasis on bone marrow adipocyte-produced adipokines, growth factors, cytokines, chemokines, and fatty acids providing the conditions for the preferential growth and migration of malignant plasma cells and contributing to hematopoiesis supression, bone tissue resorption, angiogenesis activation and immunosuppression.

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is being widely applied as a therapy for hematological malignancies. The long-term outcome of allo-HSCT depends directly on the ability of cytotoxic T-lymphocytes to recognize and eliminate the residual tumor. CTLA-4 is one of the regulatory proteins that provide control over the development of the immune response. Polymorphisms in the CTLA4 gene can affect its function and the efficiency of the antitumor response.
The objective: to study the effect of non-synonymous single nucleotide polymorphism (nsSNP) c.49A>G in the donor CTLA4 gene on tumor control in the recipient of allogeneic hematopoietic stem cells (HSC).
Materials and methods. Donors of HSC were genotyped for nsSNP c.49A>G in the CTLA4 gene by the real-time polymerase chain reaction using the allele-specific primers. Genotyping data was validated by Sanger’s sequencing of 22 randomly selected samples. The overall survival, the event-free survival and relapse probability were calculated using the Kaplan–Mayer method. A log-rank test was used to assess the statistical significance of group disparities. A p-value of 0.05 was considered as significant.
Results. The frequencies of the CTLA4 gene c.49A>G polymorphism alleles in the observed population (102 healthy donors of HSC) correspond to the frequencies obtained by the “1000 genomes” project for the European population. The effect of the donor CTLA4 polymorphism on the tumor control was evaluated on the cohort of patients with acute leukemia after human leukocyte antigen (HLA) matched HSCT from an unrelated donor. It was shown, the three-year relapse-free survival was significantly lower for those patients who received grafts from a donor with the homozygous A/A state of nsSNP c.49A>G (p = 0.01), it was 12.7 % versus 62,8 % in group with c.49A>G G/G and A/G donor genotypes. The incidence of relapse was also significantly different for the group with A/A genotype and for the group with G/G or A/G genotypes of the nsSNP and equaled to 83.7 and 29.3 % respectively (p = 0.03).
Conclusion. Patients with acute leukemia, who underwent allo-HSCT from unrelated completely HLA-matched donors with c.49A>G G/G or A/G genotypes have the significantly lower risk of relapse than patients whose donors had the A/A genotype. These results suggest practicability of the nsSNP genotyping for the optimal donor selection.