Tyrosine kinase inhibitors have radically changed the course of chronic myeloid leukemia, significantly increasing survival and reducing the risk of disease progression. Nearly 50–70 % of patients achieve a consistently low or undetectable level of minimal residual disease – a deep molecular response. The long-term tyrosine kinase inhibitors treatment in about one-third of patients is accompanied by toxicity which impairs the quality of life. Therefore, the safe treatment discontinuation is relevant. The results of clinical trials have shown 40-60% possibility of maintaining treatment-free remission in patients with long-term deep molecular respons; however, all patients with molecular relapse regain molecular remission after the resumption of tyrosine kinase inhibitors therapy. Currently, clinical and biological factors associated with maintaining treatment-free remission are being studied. It is assumed that cessation of tyrosine kinase inhibitors therapy can improve the quality of life, but approximately 30 % of patients are reporting musculoskeletal pain – so called “withdrawal syndrome” – that begins or worsens after stopping tyrosine kinase inhibitors therapy. The mechanisms for the development of this phenomenon are currently unclear. Thus, many aspects concerning treatment-free remission require to be studied, which determines the importance of clinical trials in this area.

Due to the pronounced polymorphism of stomach MALT-lymphoma endoscopic manifestations, often mimicking inflammatory changes of various etiologies, difficulties arise in the timely diagnosis of this disease. The alertness of the endoscopist and the use of integrated approaches to endoscopic diagnosis, taking into account the existing criteria for differential diagnosis, will undoubtedly improve the results of treatment.

Background. In addition to anti-HLA-I and anti-HPA-antibodies and specific cytotoxic T-lymphocytes, another cause of immune refractoriness to donor's platelet transfusions could be a platelet-associated different classes immunoglobulins PAIg (G, M, A) and C3 / C4‑components of complement system (PAC3, PAC4). These markers can be detected by flow cytofluorometry of double-stained platelets. The fixation density of immunoglobulins and components of complement systems were measured by the mean fluorescence intensity (MFI).

Objective: to study additional factors that aggravate the course of refractoriness to donor's platelet transfusions in patients with aplastic anemia (AA) and hemoblastosis.

Materials and methods. 77 patients (AA – 47, myelodysplastic syndrome (MDS) – 10, acute myeloid leukemia (AML) – 20) admitted to National Research Centre for Hematology during 11.09.2016–04.28.2018 were enrolled in the study. M / f ratio was 33 / 44, median age was 36 yrs. (19–71 yrs.). Plasmapheresis and cross-matching for PRP selection were used for patients with refractoriness to donor's platelet transfusion. PAIg (G, M, A) and PAC3 / C4 detection and density (MFI) were evaluated in all patients by flow cytofluorometry of doublestained platelets (CD41a-PE; IgA, M, G-FITC; C3 / C4‑FITC) and MFI measurement. Patients with AA were investigated on different stages of therapy and if refractoriness to donor's platelet transfusion is developed. Blood donors (n = 28) MFI measurement results were established as negative control.

Results. It was found that MFI PAIgG/M/А and PAC3/С4 was higher in all groups of the patients (АА, MDS, AML), as compared with donors. MFI of PAIgM and PAIgA in patients were significant higher than MFI of PAIgG and PAC3 / C4. Combination of PAIgM / A, PAIgM / C3 / C4 and PAIgA / C3 / C4 were more frequent. Multiple transfusions of PRP were associated with PAIgA and PAC3 detection. Development of refractoriness to donor's platelet transfusions was accompanied by alloantibodies (HLA-I, HPA) and PAIgM, PAC4 detection. In patients of AA group during development of refractoriness to donor's platelet transfusions and multiple infection complications the high density of PAIgM and PAIgA were identified. Relapse of AA was accompanied MFI of PAC3 density increment.

Conclusion. In addition to application of a certain transfusion therapy algorithm it is also necessary to detect PAIg (G, M, A) and PAC3 / C4 for prediction of severe refractoriness to donor's platelet transfusions.

Background. Rhesus phenotype has been determined in 404 persons which have problems with blood groups identification. Genetic typing of antigen RhD variants was performed in 73 individuals. Objective of the work was to give molecular and serological characteristics of the antigen RhD weak types.

Materials and methods. Method of rhesus phenotype determination in direct agglutination test on plane by using of anti-D, anti-C, anti-c, anti-Cw, anti-E and anti-e monoclonal antibodies; gel method of rhesus phenotype determination; methods of genetic typing of RhD; methods of antigen RhD determination in the classic indirect antiglobulin test and in the gel indirect antiglobulin test; method of antigen RhD determination in the saline agglutination test.

Results. Serological methods identified 73 red blood samples with the weakened expression of RhD antigen. Molecular methods showed the reasons of weakness of antigen expression. Three RHD*D weak types which are common in Russians (RHD*D weak type 1–3) were identified and for the first time 3 types were found – RHD*D weak type 67, RHD(G255R) and RHD(JVS5-38del4). Serological characteristic of RhD weak types was given. It was shown that combined using of monoclonal antibodies in direct agglutination test and in gel is the most effective serological method of the antigen variants detection. Red blood cells with weak RhD antigens can be recognized by weakness or absence of agglutination with monoclonal antibodies on plane if agglutination in gel was 3+4+.

Conclusion. Concrete weak RhD variants can be determined only by genetic typing. Serologically weak antigen variants can be detected by using of at least two series of monoclonal antibodies or by using of two different methods (it is preferable).

Background. The course of lymphoproliferative diseases, in which the proliferation of a malignant clone is accompanied by the secretion of paraproteins, is often complicated by kidney damage. Perhaps kidney damage is associated with the physicochemical properties of monoclonal proteins.

The objective of the study was to determine the relationship between the type of monoclonal paraprotein, its level of secretion, and kidney damage in lymphoproliferative diseases

Materials and methods. A retrospective analysis of the data of 108 patients with lymphoproliferative diseases accompanied by paraproteinemia and kidney damage was performed. The age of the patients was 31–86 years (median 62.5 years). 78 out of 108 patients were diagnosed with chronic kidney disease (CKD). CKD was diagnosed in accordance with the clinical guidelines of KDIGO 2012.

Results. In patients with multiple myeloma, stage III CKD was diagnosed in 28 (35.9 %) cases, stage IV – in 14 (17.9 %), stage V – in 19 (24.4 %). High risk group for CKD included 10 (9.3 %) of 30 patients without CKD. 91 patients were diagnosed with concomitant diseases predisposing to the development of kidney damage. In the group of patients with paraproteinemic hemoblastosis in combination with CKD, the vast majority were patients with the presence of IgGκ and IgGλ blood paraproteins, free light chains (FLC), and Bence-Jones protein (BJ) in the urine. At the same time, patients with the secretion of IgDλ, IgAλ, IgAκ and IgMκ paraproteins were much less common. The highest level of pathological Ig of all classes and their structural components and fragments was observed in patients with stage III CKD, which is also characteristic of other laboratory markers in CKD. A negative correlation of glomerular filtration rate (GFR) with FLCκ in the blood (r = –0.21), GFR with BJκ (r = –0.35), GFR with FLCλ in the blood (r = –0.13), GFR c BJλ, which indicates a tendency to damage the kidneys of FLC and protein BJ.

Conclusion. In patients with lymphoproliferative diseases accompanied by monoclonal secretion of paraprotein and kidney damage with the development of CKD, in most cases IgGκ, IgGλ, FLCκ and FLCλ were determined in the blood, and protein BJ in urine. IgAκ, IgAλ, IgMκ, IgMλ, IgDλ paraproteins were determined much less frequently in serum. The highest level of pathological Ig and their structural components was observed in patients with stage III CKD. No association with quantitative level, type of paraprotein, and kidney damage was found. The role of FLC and BJ protein in the development of nephropathy is noted. The results of the study also show that with the development of the disease and kidney damage with subsequent progression of the stage of CKD in patients with lymphoproliferative diseases and proteinemia, there is a tendency to a temporary decrease in proteinuria and a compensatory increase in the number of paraproteins in the blood. This can be considered as one of the compensatory pathophysiological mechanisms of the protective function of the kidneys.

In chronic lymphocytic leukemia, the risk of second tumors including hematological malignancies, with which the use of purine nucleosides and alkylating agents in treatment of chronic lymphocytic leukemia is most often associated, is significantly increased. Concurrent detection of this disease and various hematological tumors is a rare occurrence in hematological practice. Use of cytogenetic method or analysis allows to differentiate between 2 tumors and confirm differences in genetic abnormalities in different clones and on different levels of cell differentiation. This article presents a clinical case of simultaneous chronic lymphocytic leukemia and myelodysplastic syndrome with 2 clones with different cytogenetic abnormalities: partial trisomy of chromosome 12 and deletion of the long arm of chromosome 5 formed at different levels of cell differentiation.

Mortality rates approaching 60 % have been reported in hematological patients with infections caused by carbapenemase-producing Enterobacterales. The incidence of these infections is rapidly increasing, whereas the therapeutic options are limited. This review represents characteristics of infections caused by carbapenemase-producing Enterobacterales in patients with hematological disorders, highlights risk factors and management options of these infections.

The objective of the study was to evaluate the effectiveness of empirical therapy with anidulafungin in patients with invasive candidiasis in real clinical practice in Russian healthcare institutions.

Materials and methods. In a prospective multicenter (n = 23) ERA study in 2015–2017, 92 adult patients with invasive candidiasis were included. Depending on the type of anidulafungin administration, patients were divided into 2 comparable demographic groups. In the 1st group (n = 52; median age 50.5 ± 13.9 years (19–75 years); men ‒ 62 %), invasive candidiasis was microbiologically confirmed after the initiation of empirical anidulafungin therapy. In the 2nd group (n = 40; median age 47.15 ± 18.01 years (18–98 years); men — 65 %), patients received anidulafungin only after microbiological confirmation of invasive candidiasis. The groups did not statistically differ in risk factors, etiology of invasive candidiasis, the frequency of various organs damage, and also in APACHE II and SOFA score at the time of anidulafungin administration.

Results and conclusion. Overall survival on the 30th day after laboratory confirmation of invasive candidiasis was statistically significantly higher in the empirical therapy group (66 % vs 58 %; p = 0.04 416). In addition, the empirical anidulafungin therapy was lead to a significant decrease in the duration of stay in intensive care units (13.5 ± 19.7 days vs 21 ± 15 days) and the total treatment time (22 ± 18 days vs 29 ± 21 days).

Objective: to assess the economic outcomes of using anidulafungin (Eraxis®) in comparison with the recommended treatment regimens in adult patients with invasive candidiasis.

Materials and methods. The economic impact assessment was carried out using “cost–effectiveness” analysis and “budget impact” analysis. “Cost–effectiveness” and “budget impact” analyses were performed in Microsoft Excel model.

Results. An analysis of the effectiveness showed that the use of anidulafungin is characterized by higher survival (79.25 % vs 66.17 % for caspofungin and 60.84 % for mikafungin). The cost of anidulafungin was 377.7 thousand rubles, which is comparable with the course of caspofungin and 61 % lower than the cost of micafungin therapy. “Cost–effectiveness” analysis showed that the use of the anidulafungin in the treatment of invasive candidiasis is pharmacoeconomically effective and has a “cost–effectiveness” ratio comparable to caspofungin in terms of the effectiveness of therapy for 7 days and exceeds it in terms of the cost of preserving the patient»s life by 14.5 %. Compared to micafungin, anidulafungin is both more economical and more effective in terms of preserving the patient's life, reaching an advantage of up to 45 %. An analysis of the impact on the budget showed that with the complete replacement of the currently used treatment regimens in the target population of 11,840 patients with invasive candidiasis with anidulafungin, it is possible to reduce the burden on the budget of the healthcare system to 17 % or 1458.6 million rubles in year. The average savings in the 3‑year study horizon, taking into account the gradual switching of 25, 50 and 75 % of the target patient population, amounted to 1277.9 million rubles per year or 14.4 %. A sensitivity analysis confirmed the results.

Conclusion. Based on results, it can be concluded that the use of the drug anidulafungin (Eraxis®) in patients with invasive candidiasis is economically the preferred option compared to the use of current antibiotic therapy regimens.