Background. Primary immune thrombocytopenia (ITP) is an orphan disease characterized by decreased platelet count in the peripheral blood which in some cases can cause bleeding of varying severity. Currently, the use of thrombopoietin receptor agonists (TPO-RAs) is recommended as the second line therapy for ITP as it allows to achieve high platelet response (PR), including complete, in 73 % of cases of chronic ITP and in 87 % of cases of newly diagnosed disease. The mechanism of action differs for different TPO-RAs. Given this fact, in cases of resistance or intolerance to therapy with one TPO-RA, attempts are made to switch to another. The effectiveness of this approach for overcoming ITP resistance varies from 50 to 93 % according to various publications. Aim. To assess the ability to achieve and maintain PR by switching from one TPO-RA to another in cases of resistance to the previous TPO-RA used in the second or subsequent lines of therapy. Materials and methods. The analysis included 59 patients who were resistant (in 2 cases intolerance was also noted) to TPO-RA therapy (received after standard therapy) who were prescribed TPO-RA treatment with a different mechanism of action: switch from romiplostim to eltrombopag (25 patients) or vice versa (34 patients). Both groups were comparable in terms of demographic characteristics and median platelet level at the time of TPO-RA switching. Results. PR was obtained in 76 % of cases, including complete response in 54 %, as a result of switching from one TPO-RA to another in 59 patients. Among 34 patients switched from eltrombopag to romiplostim, PR was achieved in 31 (91 %) patients, including complete response in 22 (65 %). Romiplostim was switched to eltrombopag in 25 patients, PR was achieved in 14 (56 %) with complete response in 10 (40 %). Conclusion. The study showed that PR can be achieved and maintained through switching from one TPO-RA to an alternative.

Background. Currently, targeted therapy is the most promising for the treatment of myelofibrosis (MF). Today, the results of many years of experience with the use of ruxolitinib, including outside randomized trials and the identification of predictors of its effectiveness are important.Aim. To evaluate the results of long-term ruxolitinib therapy in patients with primary and secondary MF resistant to standard treatment and compare the effectiveness of MF targeted therapy in patient groups depending on age, gender, clinical, laboratory and morphological parameters.Materials and methods. The prospective study included 206 patients (95 (46 %) men and 111 (54 %) women aged 18–84 (mean 64) years) with MF in the chronic phase who received ruxolitinib: 154 (75 %) with primary MF, 39 (19 %) – with post-polycythemic, 13 (6 %) – with post-thrombocythemic. The median duration of chronic myeloproliferative disease from diagnosisto prescription of ruxolitinib was 75 (1–432) months. According to DIPSS (Dynamic International Prognostic Scoring System), 15 % of patients were classified as high risk, 35 % as intermediate-2, 33 % as intermediate-1, and 17 % as low-risk. 44 % of patients had MF3, 49 % – MF2, 7 % – MF1. 71 % of patients had JAK2 V617F mutation, 3 % – MPL, 19 % – CALR, and in 7 % triple negative status was detected.Results. The median duration of ruxolitinib therapy was 24 (1–116) months. Clinical and hematological response at 1 month: complete and partial response – 14 %, clinical improvement – 20 %, stabilization – 57 %; at 3 months – 21, 34, 36 %, at 1 year – 34, 21, 34 %, respectively. No response was obtained in 18 % of patients. The median allele burden of JAK2 V617F during observation decreased more than twice from the initial value in half of the patients. The median of progression-free survival (PFS) from the start of ruxolitinib therapy was 28 months, the median of overall survival (OS) has not been achieved. PFS at 1 year of treatment was 68 %, at 2 years – 56 %, at 3 years – 46 %, at 5 years – 32 %, OS – 87, 75, 68, and 54 %, respectively. Among many factors analyzed before starting ruxolitinib therapy, the following ones had statistically proofed significance for PFS: age, DIPSS risk level,therapy with hydroxycarbamide, interferon, white blood cell count, platelet count, hemoglobin level, and degree of fibrosis. For OS,the following factors were significantly important: age, risk level according to DIPSS,type of MF, interferon therapy, white blood cell count, platelet count, hemoglobin level, and degree of fibrosis.Conclusion. The long-term effectiveness of ruxolitinib therapy for primary and secondary MF has been demonstrated. Gender, age, clinical, laboratory, and morphological prognostic factors of ruxolitinib therapy efficiency in MF have been identified.

Patients with relapsed or refractory (r/r) DLBCL, primary mediastinal B-cell lymphoma and early relapse (up to 2 years) FL have a poor prognosis and short overall survival. Standard second-line chemotherapy for patients under 60-65 years old with r/r DLBCL includes intensive chemotherapy courses with platinum drugs and autologous stem cell transplantation (ASCT). It is known that response to therapy is achieved only in half of patients against the background of standard chemotherapy. Addition of new targeted drugs can improve treatment outcomes. This paper presents the first results of adding Venetoclax to chemotherapy in patients with r/r aggressive B-cell lymphomas.

Background. Thrombopoietin receptor agonists (TORAs), which can imitate the biological effect of thrombopoietin, have shown high efficacy in a number of clinical studies and real clinical practice in patients with resistant primary immune thrombocytopenia (IT). It seems extremely relevant to evaluate the success of using various TORAs in a longterm nonrandomized study and their comparative effectiveness.Aim. To evaluate the longterm efficacy of TORAs (romiplostim and eltrombopag) in patients with primary IT who are resistant to standard therapy, and to determine the clinical and hematological factors predicting the efficacy of TORAs therapy.Materials and methods. The study included 456 patients with primary IT (127 (28 %) men and 329 (72 %) women) who were resistant to standard therapy. atients received TORAs therapy at the otkin Hospital. The median age at the start of TORAs therapy was 59 (9–91) years. Romiplostim was received by 339 patients (95 (28 %) men and 244 (72 %) women), eltrombopag – 117 (32 (27 %) men and 85 (73 %) women).Results. The median duration of TORAs therapy was 78 (1–583) weeks for romiplostim and 59 (1–572) weeks for eltrombopag. uring the TORAs therapy the platelet response was obtained in 89 % (n = 405) of cases in total group of IT patients, in the romiplostim group – in 90 % (n = 306), in the eltrombopag group – in 85 % (n = 99). y the time of data analysis in the total cohort of IT patients, 55 % (n = 253) of patients maintained a sustained platelet response, with a median duration of 159 (2–655) weeks. Among patients receiving romiplostim, these parameters were 59 % (n = 200) and 149 (2–655) weeks, for eltrombopag – 45 % (n = 53) and 240 (24–565) weeks, respectively. The 10‑year overall survival rate with TORAs therapy, regardless of the drug chosen, was 86 %. Negative predictors of achieving a platelet response to romiplostim therapy were identified: ≥2 lines of previous therapy (p = 0.03), a history of splenectomy (p = 0.02). No negative predictors of platelet response to eltrombopag therapy were identified.Conclusion. The longterm efficacy of 2 drugs of the same therapeutic class (TORAs), romiplostim and eltrombopag, in patients with resistant IT was demonstrated in a direct comparative analysis in a nonrandomized study. Clinical and hematological factors predicting the longterm effectiveness of romiplostim were identified.

Aim. To assess the stability of clinical remission in patients with primary immune thrombocytopenia (ITP) after withdrawal of thrombopoietin receptor agonists (TPO-RAs). Materials & Methods. The study enrolled 456 patients with primary ITP who received second- and subsequent-line TPO-RA treatment. Complete platelet response (PR) was achieved in 338 patients, the therapy was discontinued in 116 of them. The present prospective clinical study started in 2014 and focused on the data of these 116 patients. Among them, there were 27 (23 %) men and 89 (77 %) women. By the time of TPO-RA therapy onset, the median age of the patients was 60 years (range 13–87 years), on ITP diagnosis date it was 52 years (range 1–80 years). Results. By the time of data analysis, 59 % of patients sustained PR after TPO-RA withdrawal. The median PR duration after TPO-RA withdrawal was 230 weeks. Romiplostim and eltrombopag recipients showed no significant differences in the survival rates without PR-loss after TPO-RA withdrawal. In the present study, the maximum PR duration achieved 9.5 years. The mid-term assessment of PR status was carried out in 3, 6, 12, 24, and 30 months after TPO-RA withdrawal and showed 99 %, 94 %, 83 %, 72 %, and 70 %, respectively. The number of previous therapy lines significantly affected the survival rates without PR-loss (p = 0.011). The age of patients, prior splenectomy, TPO-RA treatment duration, time to different PR levels on therapy, PR duration on TPO-RA therapy, and platelet count upon TPO-RA withdrawal showed no significant effect on this parameter. After PR-loss, TPO-RAs were administered again to 31 (27 %) patients. Repeated PR was achieved in 26 (84 %) of them. Conclusion. TPO-RA administration yields multi-year off-treatment remission in some patients with primary ITP. Upon therapy discontinuation, 59 % of patients with complete PR sustained PR for 3 months to 9.5 years. Stable PR after TPO-RA withdrawal significantly correlated with only one of the studied prognostic parameters, i.e., the number of previous therapy lines.

Background. Mastocytosis is a heterogeneous group of diseases that are characterized by excessive proliferation and accumulation of clonal (neoplastic) mast cells in one or more organs. Advanced variants of systemic mastocytosis (aggressive systemic mastocytosis, systemic mastocytosis associated with hematological neoplasm, and mast cell leukemia) are characterized by infiltration of organs by mast cells, which leads to organs dysfunction. Such patients require a more active approach and the use of cytoreductive therapy. Available therapeutic options include imatinib, interferon-alpha, cladribine. Only one of the targeted drugs is registered in Russia – midostaurin. Midostaurin is a potent multikinase inhibitor that is active against KIT regardless of mutation status. Midostaurin has shown its effectiveness in clinical trials, however, we know that data from real clinical practice often differ from clinical studies due to the characteristics of patients (preserved comorbid status, stable disease parameters) traditionally included in clinical trials. Aim. To evaluate the effectiveness and safety of midostaurin in patients with advanced variants of systemic mastocytosis in real clinical practice. Materials and methods. This work analyzed 13 patients (7 (54 %) men and 6 (46 %) women) who received midostaurin therapy for systemic mastocytosis (aggressive systemic mastocytosis – 9 (69 %), systemic mastocytosis associated with a hematological neoplasm – 4 (31 %)). The median age of patients when the diagnosis was verified was 73 (61–87) years, the median age when midostaurin was prescribed was 74 (61–88) years. According to the International prognostic scoring system for mastocytosis (IPSM) based on clinical variables, patients are classified as follows groups: SM1 – 1 (8 %) patient, SM2 – 3 (23 %), SM3 – 8 (61 %), SM4 – 1 (8 %). Results. As a result of therapy, clinical improvement was achieved in 10 (77 %) patients, and stabilization in 3 (23 %) patients. During midostaurin therapy, grade I–II adverse events were noted from the gastrointestinal tract: nausea in 5 patients (38 %), vomiting in 2 (15 %), diarrhea in 6 (46 %). Hematological toxicity of grade I–II was also observed: anemia in 6 (46 %) patients, thrombocytopenia in 5 (38 %) patients. The median overall survival in the group was not achieved. The 2-year overall survival rate was 75 %. Conclusion. The study results suggest the potential efficacy and safety of midostaurin in patients with aggressive systemic mastocytosis and systemic mastocytosis associated with hematological malignancies.

Background . Treatment results in patients with relapsed and refractory acute myeloid leukemia (AML) remain unsatis‑factory. Treatment options for these patients are limited. Aim . To retrospectively analyze the efficacy and safety of combined therapy with hypomethylating agents and venetoclax (VenHMA) in patients with relapsed AML and also to compare the results with the cohort of patients who received azacitidine as a monotherapy. Materials and methods . The study included patients with relapsed AML, over 50 years old, who received VenHMA therapy from 01.09.2019 to 01.06.2022 and azacytidine monotherapy from 01.03.2016 to 01.06.2022. In total we identified 38 patients who received VenHMA and 30 patients who received azacytidine alone. Results . The median age of patients in the VenHMA cohort was 66 years (range 51–84). The median number of previous therapy lines was 1.5 (range 1–3), and 12 (32 %) patients had AML evolving from prior myelodysplasia. The median follow-up was 6.2 months, with 20 patients monitored for more than 6 months. Complete response was obtained in 13 (34 %) patients, complete remission with incomplete recovery in 8 (21 %), leukemia-free state in 2 (5 %) patients. Thus, overall response was achieved in 23 (60 %) patients. The median time to achieve overall response was 2.6 months. At the time of the final analysis, 16 patients were still receiving treatment. The median of relapse-free survival in patients with response was not achieved; the median of overall survival was 15.6 months. The groups of patients receiving VenHMA or azacitidine alone were comparable in terms of the main characteristics, with the exception of initial thrombocytopenia <50 × 109/L, which was more frequently encountered in VenHMA cohort (47 % versus 20 %). The median time to the next therapy in the VenHMA group was 10.16 months, in the azacitidine group 6.7 months (hazard ratio (log-rank) 2.02; 95 % confidence interval 1.15–3.5; p = 0.013). The median overall survival in the VenHMA group was 15.6 months, in the azacitidine group 8.5 months (hazard ratio 2.49; 95 % confidence interval 1.36–4,5; p = 0.0044). In a multivariate analysis of factors, associated with adverse outcome (age >65 years, secondary AML, azacytidine monotherapy) only secondary AML was a significant factor for overall survival. Conclusion . The results of our retrospective study show the superiority of the combination regimen of venetoclax and azacitidine in the treatment of AML relapses, both in terms of the quality of remissions and their duration. Patients with relapse and primary refractory AML represent cases of poor cytogenetic prognosis, and have an aggravated somatic status. To date, the use of the VenGMA regimen allows finding the optimal balance between the intensity and toxicity of therapy.

Background. Targeted therapy is the most promising in the treatment of myelofibrosis, but it is necessary to search for the reasons limiting its effectiveness. There are known factors negatively affecting the development of myelofibrosis, but data on their negative impact in the context of targeted therapy are scarce.Aim. Assessing the impact of cytogenetic and genetic abnormalities on the course and therapy results for primary and secondary myelofibrosis during ruxolitinib therapy.Materials and methods. The prospective study included 106 patients with myelofibrosis in the chronic phase (53 (50 %) men and 53 (50 %) women) who received ruxolitinib at the Moscow City Hematology Center, S.P. Botkin City Clinical Hospital. The median age of patients was 62 (18–84) years. The median disease duration before initiation of ruxolitinib therapy was 79 (1–432) months. Before therapy, genetic studies were performed, including next-generation sequencing. The median duration of ruxolitinib therapy was 33 (1–111) months. The influence of the cytogenetic landscape, driver mutations, allele burden of JAK2 (over time) and CALR, additional mutations on the dynamics of symptoms, spleen size, achievement of hematological response, overall survival, progression-free survival, survival without blast crisis and without progression of myelofibrosis with targeted therapy was assessed.Results. The studied genetic factors did not have a significant correlation with hemogram parameters. The hematological response in patients with JAK2 and CALR mutations compared favorably with the response in the groups with the MPL mutation and triple negative status (TNS). Higher hematological response rate was obtained in the group with initially low allele burden <50 % of JAK2 or CALR. Significant differences in 5-year overall survival were found between groups of patients with TNS and JAK2 and CALR mutations (p <0.05); with CALR allele burden <50 % and ³50 % before initiation of ruxolitinib therapy (p = 0.01); the presence or absence of positive dynamics of the JAK2 allele burden during treatment (p <0.05); additional mutations assigned to different pathogenicity groups (p <0.05); with different number of pathogenic mutations (1 or ³2), the presence or absence of pathogenic mutations in the ASXL1 (p = 0.002) and SETBP1 (p = 0.00001) genes. The 5-year progression-free survival was significantly different in cohorts of patients with or without positive dynamics of the JAK2 allelic load during treatment (p <0.05); additional mutations assigned to different pathogenicity groups (p <0.05); with a different number of pathogenic mutations (1 or ³2), the presence or absence of a pathogenic mutation of the SETBP1 gene (p = 0.003). Progression-free survival did not correlate with the type of driver mutation or its absence; however, all patients with TNS died from myelofibrosis progression. Significant differences in 5-year blast crisis-free survival were observed between groups with JAK2 and MPL mutations (p = 0.001), JAK2 and TNS (p = 0.002); difference in 5-year survival without progression of fibrosis – between groups with pathogenic and benign (p = 0.031); uncertain and benign (p = 0.001) mutations.Conclusion. The study identified genetic markers associated with decreased efficacy of ruxolitinib therapy.

New Bruton’s tyrosine kinase (BTK) inhibitors caused drastic modifications in the therapy of chronic lymphocytic leukemia (CLL). Ibrutinib, the first in its class BTK inhibitor, showed high efficacy in many clinical studies. However, the treatment with BTK inhibitors as monotherapy must not be discontinued. Ibrutinib monotherapy inevitably leads to BTK inhibitor resistance and severe adverse events, which often results in treatment failure. Inhibitor BCL-2 venetoclax combined with BTK inhibitor can increase the therapy efficacy due to the synergetic effect of these agents on different CLL cell populations. Combined therapy potentially providing fixed-duration treatment can yield deeper responses. The present review focuses on ibrutinib and venetoclax combination, summarizes the latest data from clinical studies, and deals with feasibility of combined therapy in terms of its efficacy and safety profile.

Aim. To study the quality of life in patients with chronic immune thrombocytopenia (ITP) in the process of romiplostim therapy and to assess the efficacy and safety of this drug in real-world setting. Materials & Methods. The study enrolled adult patients with the confirmed chronic ITP diagnosis and indications for romiplostim therapy. Clinical parameters, RAND SF-36 and FACT-Th6 quality of life as well as FACIT-Fatigue scores were evaluated prior to romiplostim administration vs. 3, 6, and 12 months after the treatment onset. Patient satisfaction checklist was also administered at all study points after the start of therapy. The clinical efficacy of romiplostim was analyzed along with assessing response and time to response. To study the quality of life and fatigue changes, the Generalized Estimating Equation (GEE) method was used during the observation period. Significant fatigue changes were determined and compared in terms of the perception differences from patient’s and physician’s perspective. Results. The study enrolled 60 chronic ITP patients treated with romiplostim in the real-world setting (mean age 51.9 years, 70 % women). The median thrombocyte count prior to romiplostim therapy was 18.5 × 109/L (interquartile range 10.8–22.3 × 109/л). On the enrollment date, 90 % of patients showed hemorrhagic syndrome. Overall response to romiplostim therapy was 98.3 % (complete response was achieved in 93.3 % of patients). After 6 months of therapy, 89.5 % of patients preserved response. After 3 months of therapy, hemorrhagic syndrome was eliminated in 81 % of patients, after 6 months the same was achieved in 93 % of patients. The median time to response was 4.4 weeks (95% confidence interval 3.6–5.3 weeks). Adverse events of grades 1/2 associated with romiplostim were reported in 6.7 % of patients. On romiplostim therapy, pronounced positive changes in quality of life were shown by all scales of the general questionnaire SF-36 and the targeted questionnaire FACT-Th6 (p < 0.001). The clearest improvements were observed in role-physical and role-emotional functioning. Already after 3 months of therapy, a considerable fatigue reduction was observed and sustained for the next 6 and 12 months of romiplostim administration (p < 0.001). During the therapy, the proportion of patients with fatigue impacting various aspects of functioning became considerably smaller. The vast majority of patients (85 %) were satisfied with the treatment. Discrepancies between patients’ and physicians’ evaluations of fatigue were also identified during the treatment. Conclusion. The results of the present multi-center observational study demonstrate high efficacy and safety of romiplostim for chronic ITP patients in the real-world setting. Romiplostim therapy yields considerable quality of life improvement and fatigue reduction. To optimize the patient monitoring system and patient-centered ITP treatment in the real-world setting, it is advisable to use the standardized questionnaires assessing quality of life and fatigue.

The aim of the given study is investigation of influence onosteodestruction markers and quality of life parameters of therapy with generic preparation of pamidronic acid (pomegara) in patients with multiple myeloma (MM) and lytic bone lesions. For this purpose prior to the beginning of the study and every 4 week after pomegara injection throughout 16 weeks blood СТХ (terminal crosslinking telopeptide of type I collagene) concentration and urine DPD (deoxypyridinoline) were detected. In addition monitoring of tumor symptoms intensity using MDASI (M.D. Anderson Symptom Inventory) and FACT (Functional Assessment of Cancer Therapy) questionnaires was conducted and pain intensity was also investigated using analogue scale. Study is finished in eighteen patients. Bone resorbtion markers (serum СТХ and urine DPD) have essential decreased after fourth pomegara injection to 33 % of median initial value for CTX (р < 0.05) and to 73 % – for DPD (р=ns). Statistically significant increasing of integrated quality of life parameter in comparison with initial value is registered by 12th week of treatment (р < 0.05). The majority of pomegara side effects were mild and moderate severity and preparation cancelling has not necessary. The frequency and spectrum of complications (fever, skeletal and muscular pain, etc.) corresponded to the similar parameters revealed in large controlled studies of bisphosphonate treatment in MM. Careful monitoring of renal function during pomegara treatment has not shown significant negative effect, including patients with initial renal involvement. According to data received in this restricted volume study we can conclude that pomegara treatment in patients with MM and lytic bone lesions result in decrease of bone destruction, quality of life improvement and decrease severity of pain. Drug acceptability did not principally differ from original pamidronate shown in controlled studies.

Introduction. Optimal therapy for elderly patients with chronic lymphocytic leukemia (CLL) is the subject of intensive research. Aim – to study the safety of obinutuzumab, as well as the selection of the optimal scheme of its use in patients with CLL, complicated by diabetes mellitus, renal insuffi ciency, cardiac comorbidity. Materials and methods. The study included primary patients with CLL having indications requiring therapy. The inclusion criteria were: Cumulative Illness Rating Scale, CIRS) (CIRS) > 6 and or glomerular fi ltration rate (GFR) < 70 mL/min, the lower limit of GFR was not restricted. The study focused on patients with diabetes mellitus, renal failure and signifi cant cardiac pathology. Patients with Richter’s syndrome, CNS involvement, HBs-antigen, and 17p deletion were not included. In the fi rst cycle obinutuzumab was administered at a dose of 100 or 25 mg on the fi rst day and 900 or 975 mg on the second day, then at a dose of 1000 mg on days 8 and 15. For all subsequent cycles, obinutuzumab was given at a dose of 1000 mg on day 1. The dosage of chlorambucil was 10 mg/m2 from days 1 to 7. Treatment cycles in totals of 6 were repeated every 28 days. Results. The study included 90 patients. Median age was 73.5 years, range – 60–89 years, there were 49 men (54 %) and 41 women (46 %). Twenty-four patients (27 %) had stage C, IGHV unmutated status was detected in 76 % of patients. The median creatinine clearance was 48.6 mL/min (25–110). The median CIRS score was 3 (range – 1–14). Thirty-one patients (34 %) had signifi cant cardiovascular comorbidity (previous myocardial infarction, coronary artery stenting or bypass, HF ≥ II NYHA, peripheral artery disease) as well as hemodynamically signifi cant valvular disease. Fifteen patients (17 %) had diabetes mellitus and 71 patients (79 %) had creatinine clearance < 70 ml/min. Infusion reactions to obinutuzumab grade ≥ II were reported in 29 patients (32 %). Hospitalization on the day of administration or the next day after the fi rst administration was required in 5 cases (5.5 %). Twenty-seven (30 %) patients could not complete 6 cycles. The largest number of patients (14 people, 15.5 %) stopped treatment after 1 course. The causes were the development of persistent cytopenia (n = 4), grade IV reaction to obinutuzumab (n = 3), patient’s refusal (n = 2), infectious complications (n = 2), severe tumor lysis syndrome (n = 1), acute pancreatitis (n = 1) and toxicodermia (n = 1). The leading cause of premature discontinuation on subsequent cycles was persistent neutropenia. Progression during treatment occurred in 3 patients only. Overall survival was signifi cantly predicted by CIRS (maximum discriminatory value of 3, p = 0.013) as well as GFR < 50 mL/min (p = 0.03). No other associations were identifi ed. At least 1 episode of grade III–IV neutropenia occurred in 41 % of patients. Grade IV neutropenia was associated with creatinine clearance < 60 mL/min (p = 0.05), baseline neutrophil level < 2 × 109/L (p = 0.0001), baseline monocyte level < 0.3 × 109/L (p = 0.007) and age > 70 years (p = 0.01). The effectiveness of treatment was evaluated in patients who completed at least 3 cycles of therapy. Complete remission was achieved in 26 patients (35 %), partial remission – in 41 (54 %), stabilization – in 4 (5 %), progression was noted in 3 (4 %). Sixteen patients (18 %) were not available to respond to the assessment. Minimal residual disease < 0.01 % in the bone marrow after completion of treatment was found in 17 patients (19 %), within 0.01–0.9 % – in 25 (28 %) patients. The median follow-up from the date of therapy initiation was 39.7 months (range – 0.6–72 months). The median relapse-free survival was not reached, and 2- and 3-year survival rates were 81 and 62 %, respectively. Poor relapse-free survival signifi cantly correlated with unmutated IGHV genes (HR = 2.4, 95 % CI: 1.12–5.0, p = 0.02) and partial response as opposed to complete response (HR = 3.35; 95 % CI: 1.45–7.7, p = 0.03). Conclusion. The results of our study have practical implications as obinutuzumab is actively integrated into modern treatment regimens. Infusion reactions pose a high risk of complications in elderly patients. The dose of obinutuzumab on day 1 of administration in elderly patients, should not exceed 25 mg. The G-Clb regimen may not be optimal in patients over 75 years of age due to the unpredictable risk of complications. In patients at high risk of neutropenia, it may be appropriate to consider primary prophylaxis. ClbG is an effective regimen that resulted in high rate of MRD-negative responses and prolonged relapse-free survival.

To obtain a sufficient number of hemopoietic progenitor cells (HPCs) for a rapid and stable recovery of hematopoiesis is one of the major conditions for safe high-dose chemotherapy. The paper analyses the current approaches to mobilizing and collecting HPCs, as well as the factors influencing their efficiency. By using their own large material (264 patients who had undergone mobilizing procedures), the authors have shown that none of predictors (age, a history of multiple courses of chemotherapy, peripheral blood levels of CD34+ cells at sampling, etc.) may identify patients in whom peripheral blood HPCs cannot be certainly ineffectively collected. At the same time, combined mobilization with myelostimulating factors (granulocyte, granulocytemacrophage colony-stimulating factors) and cytostatics (high-dose cyclophosphamide) yield the greatest quantities of HPCs from peripheral blood in patients with solid tumors and multiple myeloma.

Aim. To study quality of life (QoL) indicators and symptom profile as well as treatment satisfaction of patients with relapsed/refractory multiple myeloma (r/r MM) on triplet therapy based on ixazomib combined with lenalidomide and dexamethasone (IxaRd); to assess efficacy and safety of IxaRd protocol in real-world clinical practice. Materials & Methods. The study enrolled 40 patients with confirmed r/r MM diagnosis, aged > 18 years, at 18 Russian health care institutions. They received at least one line of prior therapy and were IxaRd-eligible. Clinical and QoL indicators were assessed according to the RAND SF-36, and symptoms were evaluated using the ESAS-R questionnaire prior to IxaRd therapy and in 1, 3, 6, 9, 12, 15, and 18 months after its start. Besides, patients filled out checklists for assessment of treatment satisfaction at all time-points after therapy onset. The analysis of clinical IxaRd efficacy included assessment of treatment response by IMWG 2011 criteria, as well as response duration, overall survival (OS), and progression-free survival (PFS). The analysis of IxaRd safety was based on reporting adverse events (AEs), including severe ones (SAEs). To analyze patient-reported QoL and symptom changes during follow-up, GEE was used. To determine clinically meaningful changes, an effect size was calculated. Results. The study included 40 r/r MM patients (mean age 63 ± 9 years, 65 % women). Median disease duration before IxaRd therapy onset was 55 months (range 2-99 months). 60 % of patients had IIIA/IIIB Durie-Salmon stage. With the median IxaRd duration of 7.5 months, clinical benefit rate was 71.8 %. Complete response was reported in 7.7 % of patients, stringent complete response in 2.6 % of patients, very good partial response in 5.1 % of patients, partial response in 30.8 % of patients, and minor response was achieved in 25.6 % of patients. Stable disease was reported in 15.4 % of patients, and disease progression was identified in 10.3 % patients, including immunochemical relapse in 1 patient. The median response duration was 16.3 months (95% confidence interval [95% CI] 15.4-17.3 months), the median PFS was 10.6 months (95% CI 6.3-16.3 months). The median OS was not reached; the 1-year OS after IxaRd therapy onset was 85.2 % (95% CI 71-99 %). AEs on IxaRd therapy were reported in 55 % of patients, SAEs were reported in 3 (7.5 %) patients. Positive QoL changes were observed on IxaRd therapy. QoL improvement was meaningful in terms of physical functioning, role-physical functioning, general health, vitality, and mental health, compared to baseline. Moreover, a considerable decrease of pain, fatigue, and nausea was revealed. On the whole, 87.5 % of patients were satisfied with the triplet IxaRd therapy. Conclusion. The results of the present pilot study demonstrate efficacy and safety of the triplet IxaRd therapy (all per os) in real-world clinical practice from r/r MM patients’ and physicians’ perspective. Our data testify to the importance of patients’ feedback in the evaluation of therapy efficacy.

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disease of the blood system characterized by intravascular hemolysis, bone marrow dysfunction and an increased risk of thrombotic and organ complications. Aim - to provide relevant clinical recommendations for the provision of medical care to adults and children with PNH. Basic information. Experts from the National Hematological Society association which is focused on the promotion of hematology, transfusiology and bone marrow transplantation along with experts from the public organization, National Society of Pediatric Hematologists and Oncologists, have developed current clinical recommendations for providing medical care to adults and children with PNH. The recommendations address in detail the issues of etiology, pathogenesis, epidemiology, and clinical manifestations of the disease. Special attention is paid to the diagnosis, differential diagnosis, and treatment of PNH based on the principles of evidence.

Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement – in 21 % (n = 30), disease stabilization – in 33 % (n = 46) of cases. No response was received in 1 (1 %) patient and in 3 (3 %) cases there was progression of the disease. At the time of analysis, 81 (57 %) of 141 patients were continuing the ruxolitinib treatment. The fatal outcome in 33 (22 %) patients was associated with concomitant diseases, among which 20 (14 %) died from proven COvId-19 infection. Overall survival: 1-year 81 %, 2-year 73 %, 5-year 50 %. Overall survival excluding deaths due to COvId-19: 1-year 92 %, 2-year 85 %, 5-year 70 %. Massive splenomegaly and a high degree of fibrosis were unfavorable predictors of prognosis of overall survival.Conclusion. Target therapy with Janus kinase inhibitor ruxolitinib has demonstrated high efficacy in patients with myelofibrosis in routine clinical practice. The most rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. Tolerability of ruxolitinib therapy was generally satisfactory. The overall and progression-free survival rates in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was consistent with the results of international multicenter clinical trials.

Background. The treatment of elderly patients with acute myeloid leukemias (AML) is one of the most formidable challenges in oncohematology. Hypomethylating drugs combined with venetoclax show relatively high efficacy and lower toxicity in elderly AML patients. Aim. To retrospectively analyze the efficacy and tolerability of the combined azacitidine/venetoclax therapy in AML primary patients of older age as well as to determine a spectrum of issues related to the implementation of this regimen in real-world clinical practice. Materials & Methods. The retrospective analysis enrolled a cohort of patients followed-up at the Botkin City Clinical Hospital (п = 35). The median age was 73 years (range 6090 years), 57 % of patients were over 70 years of age. The median follow-up duration was 5.2 months (range 1.6-42.6 months). By the time of final analysis 15 patients were still receiving the therapy. The median of overall survival was 11.1 months (95% confidence interval [95% CI] 8.1-14.1 months). The causes of death in 20 patients were AML progression (n = 3), non-COVID-19 infectious complications (n = 3), and COVID-19 (n = 10). In 4 patients the cause of death remained unidentified. Results. Complete remission (CR) was documented in 17 (48.5 %) patients; CR with incomplete hematologic recovery was identified in 9 (26 %) patients. The median time before achieving remission was 67 days (range 27-120 days). In 96 % of patients CR was achieved after 3 azacitidine/venetoclax cycles. The mean CR duration was 9.2 months (95% CI 5.7-12.6 months); the median time before loss of response was 19 months. Relapses were diagnosed in 5 patients. Neutropenia > grade 3 was identified in patients who achieved remission on subsequent therapy cycles in 100 % of cases (n = 26), anemia > grade 2 was reported in 9 (34 %) patients, and thrombocytopenia > grade 3 was detected in 13 (50 %) patients. Despite frequent neutropenia, patients with remission did not show any severe infectious complications. Conclusion. The combined azacitidine/venetoclax therapy in elderly patients yields remission in more than 70 % of cases and is not marked by any severe infectious complications, despite developing neutropenia. Due to its ease of administration and low toxicity, this regimen can be performed in outpatient units.

New guidelines on diagnosis and treatment of a primary immune thrombocytopenia (ITP) in children and adults, on the basis of modern pathogenesis conceptions and considering possibilities of hematological practice in Russia are presented. Guidelines are based on a consensus of international and Russian experts on ITP. Diagnostic features of ITP are noted and various I, II and III lines treatment, including new effective medical products which have recently appeared in Russia, in particular, trombopoietin receptor agonists (romiplostim, eltrombopag), considerably expanded conservative treatment possibilities are offered. The presented guidelines can help hematologists to develop individual schedule for each given patients with ITP and to improve patients quality of life.

High-dose chemotherapy (HDC) with autologous or allogenic hemopoietic stem cell transplantation (SCT) is successfully used in refractory, relapsed or high-risk primary aggressive non-Hodgkin's lymphomas (NHL). Results on HDC employing in follicular lymphoma, is inconclusive. Recent studies has suggested that com- bining of anti-CD20 (rituximab) with HDC (HDC-R) may successfully eliminate minimal residual disease, further delaying or preventing disease relapse and potentially extending the duration of survival after autologous SCT in patient with aggressive B-cell lymphomas. The paper discusses recent dates on HDC-R treatment strategy and presents the author's own data on the use of HDC with autologous SCT in a group of 50 patients with relapsed and primary resistant NHL (22 of them received rituximab at different stages of treatment - remission induction, stem cell collection, posttransplantation period). In all patients receiving high- dose therapy, 5-year overall survival was 40.3% and 5-year relapse-free survival was 77.5%. 5-year overall survival was 52% in patients with the B-cell pheno- type treated with HDC plus rituximab, and 21% in those treated with HDC only (p = 0.014). Treatment toxicity was comparable in both groups.

Introduction. 13q14 deletion is the most common chromosomal abnormality in chronic lymphocytic leukemia (CLL), and as the sole abnormality determines the most favorable prognosis of the disease. Using molecular genetic methods two subtypes of 13q14 deletion were identified based on the size of the lost chromosomal material: small (type I) with the involvement of the D13S319 segment containing MIR15A/MIR16-1 and DLEU1 genes and large (type II) containing centromeric region of 13q14 involving RB1 gene. Data on the impact of type I and II deletions on the course of CLL are controversial. Aim - to evaluate the prognostic significance of different variants of 13q14 deletion in CLL. Patients and methods. The study enrolled two cohorts of CLL patients. Cohort 1: 256 patients who were studied by FISH with DNA probes for detection of 13q14/D13S319, 11q23/ATM, 17p13/TP53 deletions, and trisomy 12 before immunochemotherapy. 101 patients with identified 13q14/D13S319 deletion were analyzed with a DNA probe for RB1 locus for determination of deletion size (type I or type II). Cohort 2: 28 patients at different stages of the disease with deletion 13q14 detected by FISH were studied by using combination of standard and molecular cytogenetic methods (mFISH, mBAND, arrayCGH) to clarify the structure of 13q abnormalities. Results. In Cohort 1 chromosomal aberrations were detected in 75 % of patients: 13q deletion - 52 % (isolated - 36 % of all cases and 48 % of cases with deletion), 11q deletion -19 %, +12 - 13 %, 17p deletion - 6 %. 13q14 deletion type I was detected in 56 %, type II - in 44 % of patients. Type II deletion correlated with the presence of 11q deletion (p = 0.05). Isolated deletions of type I and II were found in 61 and 39 %, respectively. Biallelic deletion was identified in 12.7 % of patients with 13q deletion. Statistically significant differences in OS were obtained in type I and II groups of patients with isolated 13q14 deletions: median OS was not reached and made 67.5 months, respectively, p = 0.05. In Cohort 2 structural abnormalities of chromosome 13 by conventional cytogenetic analysis (CCA) were identified in 50 % of cases: 13q deletion - 11 cases; translocations involving 13q14 - 6 cases. In 5 cases with biallelic deletion identified by FISH, 13q14 deletion by CCA was detected in two patients, and only in one allele. Conclusion. In general, 13q14 deletion is a cytogenetic factor of favorable prognosis for CLL but its structure is heterogeneous. Loss of tumor suppressor RB1 (type II deletion) negatively affects OS in patients treated with immunochemotherapy.