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. The effectiveness of therapy for acute T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) has significantly improved over the past decades, including through the implementation of hematopoietic stem cell transplantation (HSCT). The Russian multicenter ALL-2009 study (ClinicalTrials.gov NCT01193933) showed that performing autologous HSCT (auto-HSCT) in patients with T-ALL/LBL improves long-term results. However, the study was non-randomized and the need for auto-HSCT in clinical practice requires careful study.
Aim. To assess the significance of auto-HSCT in patients with T-ALL/LBL in the framework of ALL-2016 multicenter, prospective, randomized study (ClinicalTrials.gov NCT03462095).
Materials and methods. The study included 109 adult patients with T-ALL/LBL (m:f 82:27). Median age was 31 (18– 52) years. T-ALL was diagnosed in 88 (81 %) patients, T-LBL in 21 (19 %) patients. All patients are treated according to the ALL-2016 protocol. Using the web platform, upon completion of induction therapy (+70 days), all T-ALL/LBL patients who achieved clinical and hematological remission were randomized to the auto-HSCT arm or chemotherapy alone (CT). Centralized monitoring of minimal residual disease (MRD) in bone marrow samples was performed by multicolor flow cytometry at the control points according to the ALL-2016 protocol. Statistical analysis was performed using SAS 9.4.
Results. 87 patients with T-ALL/LBL were randomized: 44 to the auto-HSCT arm and 43 to the CT arm. Further analysis included 25 patients who underwent auto-HSCT and 36 patients receiving only CT. Three-year relapse-free survival in T-ALL is estimated at 62 % (auto-HSCT) vs. 81 % (CT) (p = 0.3422), and in T-LBL – 67 % (auto-HSCT) vs. 79 % (CT) (p = 0.59). MRD persistence on the +70^th day of therapy according to the ALL-2016 protocol was determined in 40 % of patients (autoHSCT) and in 67 % (CT) (p = 0.057). In a multivariate analysis, it was determined that T-ALL from early T-cell precursor (ETP-variant) and MRD persistence after the end of II phase induction are the main risk factors for relapse in the treatment according to the ALL-2016 protocol.
Conclusion. Performing auto-HSCT both in patients with T-ALL and T-LBL, and with MRD persistence on day +70 according to the ALL-2016 protocol did not improve long-term results. The development of new programs for the treatment of patients with MRD persistence, as well as the ETP variant of T-ALL, is of current interest.

We present a description of the difficulties in diagnosing acute megakaryoblastic leukemia in a child with Down syndrome aggravated by multiple comorbidities. In this case, a comprehensive assessment of clinical data, the results of an automatic complete blood count with a detailed interpretation of the entire range of parameters, as well as morphological and immunophenotypic bone marrow examination using an extended panel of monoclonal antibodies played a key role in the diagnosis.

Peripheral T-cell lymphoma unspecified (PTCLu) in most cases has an aggressive clinical course and is characterized by a high frequency of extranodal lesions. One of the manifestations of PTCLu, in particular Lennert’s lymphoma, is eosinophilia. Regardless of the development mechanism, eosinophilia can be accompanied by heart damage, leading to endomyocardial fibrosis, ventricular thrombosis and, in the final stage, to restrictive cardiomyopathies, which are manifestations of Loeffler’s endocarditis (LE). The presence of LE aggravates the course and prognosis of PTCLu, primarily limiting the possibilities of antitumor drug therapy. A multidisciplinary approach to managing a patient with PTCLu and concomitant LE makes it possible to diagnose and start both specific and cardiotropic therapy in a timely manner, ultimately improving the prognosis. A clinical case of a 44‑year-old patient with newly diagnosed PTCLu (Lennert’s lymphoma) and LE is presented.

Background. Multiple myeloma (MM) is a plasma cell tumour, which could be followed by formation of bone plasmacytomas. Bone plasmacytoma is plasma cells proliferate, developed in a medullar cavity, which could destroy cortical layer of a bone and escape to the surrounding tissues. Biological characteristics of tumour substrate hypothetically could influence the clinical course of MM.
Aim. To compare clinical and laboratory parameters of newly diagnosed MM depending on the presence or absence of bone plasmacytomas.
Materials and methods. A retrospective study included 40 patients with newly diagnosed MM aged from 24 to 63 years. 21 patients are diagnosed with bone plasmacytomas. In another 19 patients MM proceeded without plasmacytomas. As an induction therapy all patients were treated with bortezomib-containing regimens. 10 patients were also received immunomodulatory drugs. 34 patients underwent autologous hematopoietic stem cell transplantation (auto-HSCT).
Results. When comparing laboratory parameters at the onset of MM, patients with bone plasmacytomas showed minor lesion of bone marrow, higher haemoglobin concentration and low paraprotein secretion. When comparing MM clinical parameters it turned out that the frequency of achieving a significant antitumor response after induction therapy was reliably lower in patients with bone plasmacytomas: 28.6 % versus 68.4 % (p = 0.038). Auto-HSCT made it possible to deepen the antitumor response in group of patients with bone plasmacytomas. On +100 day auto-HSCT significant antitumor response was registered in 52.6 % of patients. For correct assessment of antitumor response the dynamics of plasmacytoma measurements is very important. When using only the data of immunochemical analysis for response assessment, the frequency of achieving a significant antitumor response is overestimated, this is not an adequate reflection of clinical situation.
Conclusion. MM with bone plasmacytomas has some clinical and laboratory features. Auto-HSCT is highly efficient method of treatment of this patient cohort. Assessment of antitumor response in patients with bone plasmacytomas only by the data of immunochemical analysis is insufficient and may serve as a reason for choosing the wrong therapeutical tactics.

This study was performed in real clinical practice settings. Our paper describes two case studies which show the difficulty of differential diagnosis of monoclonal gammopathies, multiple myeloma associated with AL-amyloidosis and primary AL-amyloidosis.

Background. The development of myelofibrosis (MF) is driven by complex molecular genetic events that include driver somatic mutations responsible for the constitutive activation of the JAK/STAT signaling pathway (JAK2, CALR, and MPL), additional mutations affecting epigenetic regulators (TET2, ASXL1, IDH1/2, etc.) and RNA splicing (SRSF2, U2AF1, SF3B1, etc.), as well as genetic aberrations that contribute to genomic instability and disease progression.

Aim. To analyze driver (JAK2, CALR, MPL) and prognostic (ASXL1) somatic mutations in patients with MF and evaluate their impact on survival.

Materials and methods. The study included 29 patients diagnosed with MF, selected by hematologists from the City Clinical Hospital No. 7 and Regional Clinical Hospital (Krasnoyarsk).

Results. 26 (89.6 %) out of 29 examined patients had some driver mutations in JAK2, CALR, MPL genes. The p.V617F mutation in the JAK2 gene was found in 20 (68.9 %) patients. Mutations in the CALR gene were detected in 4 (13.8 %) patients, mutations in the MPL gene were found in 3 patients (10.3 %). In 1 of 26 patients, 2 driver mutations were present simultaneously. 3 (10.3 %) patients were triple negative. Mutations in the ASXL1 gene were detected in 12 (41.4 %) out of 29 examined patients. Conducted targeted NGS (next generation sequencing) for 13 out of 29 patients revealed additional genetic variants that contribute to the understanding of the development mechanism and disease course. When evaluating the overall survival in the groups of patients diagnosed with MF examined by us, depending on the combination of driver (JAK2, CALR, MPL) and prognostic (ASXL1) mutations, no statistically significant differences were found (p = 0.12). This appears to be due to the small sample size. At the same time, assessment of patient survival depending on ASXL1 status showed that in the presence of mutations in the ASXL1 gene, the median survival was 45 months (range 7–120 months), while in the absence of mutations it was 48 months (range 21–359 months) (p = 0.03).

Conclusion. The results obtained allow us to assume that the presence of mutations in the ASXL1 gene is an unfavorable factor in the course of the disease.

Aim. To assess the pharmacoeconomic feasibility of using polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin and prednisolone (R-CHP) in 1^st line therapy of adult patients with diffuse large B-cell lymphoma in the Russian healthcare system, taking into account the currently used therapeutic practices in oncohematology.
Materials and methods. The design of the study is a retrospective analysis of literature data. Clinical and economic analysis (incremental cost–effectiveness analysis, case-based approach) was performed using sensitivity assessment. The sources of data on the effectiveness of the analyzed drugs were publications on clinical trials, on the cost of drugs – the state register of maximum selling prices, data from the manufacturer.
Results. An incremental cost–effectiveness analysis was performed using a case-based approach comparing the cost of progression-free life-year gained. Brentuximab vedotin, already included in the list of vital and essential drugs and provided at the expense of budgetary funds, was chosen as the reference drug. It has been established that the cost of progression-free life-year gained (ICER) with the use of polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin and prednisolone (R-CHP) in 1^st line therapy of adult patients with diffuse large B-cell lymphoma by 60.8 %, or 41.6 million rubles, lower than the cost of progression-free life-year gained when using brentuximab vedotin in combination with doxorubicin, vinblastine and dacarbazine in the 1^st line therapy of patients with CD30-positive classical Hodgkin’s lymphoma. Sensitivity assessment showed the stability of the obtained results of clinical and economic analysis to changes in the cost of drugs in compared therapy regimens. The results were sensitive to changes in the efficacy of the compared regimens.
Conclusion. The obtained results of the clinical and economic analysis demonstrated that the use of polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin and prednisolone (R-CHP) in the 1^st line therapy of adult patients with diffuse large B-cell lymphoma in the Russian healthcare system is economically appropriate.

Background. Higher rate of gram-negative bloodstream infections (BSI) have been recently documented from transplantation centers providing fluoroquinolone (FQ) prophylaxis.
Aim. To define the incidence of BSI during neutropenia according to gut mucosal colonization with resistant gramnegative bacteria and FQ administration.
Materials and methods. Of 284 allogeneic hematopoietic cell transplant recipients included in the study, 154 (54.2 %) were identified as colonized with resistant gram-negative bacteria, and 130 (45.8 %) patients as non-colonized. Resistant gram-negative bacteria included Enterobacterales with extended spectrum beta-lactamase production, carbapenem-resistant Enterobacterales, Stenotrophomonas maltophilia, and carbapenem-resistant strains of Pseudomonas aeruginosa. Colonized patients did not receive FQ prophylaxis (n = 147) except 7 patients who received FQ as sequential therapy due to residual inflammatory lung lesions. Among non-colonized patients 98 received FQ prophylaxis, whereas 32 did not.
Results. Probability of gram-negative BSI (71.4 %; p <0.0001), and extended spectrum beta-lactamase-producing Enterobacterales BSI (57.1 %; p <0.0001) was significantly higher in colonized patients receiving FQ. No significant difference was found in probability of gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (hazard ratio (HR) 35.32; 95 % confidence interval (CI) 9.15–136.44; p <0.0001) or without FQ (HR 3.44; 95 % CI 1.15–10.31; p = 0.007), omission of FQ in non-colonized patients (HR 4.03; 95 % CI 1.08–15.00; p = 0.038), and active disease before allogeneic hematopoietic cell transplantation (HR 2.17; 95 % CI 1.03–4.63; p = 0.042) were associated with higher risk of gram-negative BSI, whereas mismatched unrelated donor transplantations were associated with higher gram-positive BSI risk (HR 3.84; 95 % CI 1.63–9.08; p = 0,009).
Conclusion. Colonization with multiresistant gram-negative bacteria is a predictor of gram-negative BSI, including multiresistant pathogens, especially when FQ are prescribed during neutropenia, while in non-colonized patients FQ prophylaxis is an effective approach significantly reducing gram-negative BSI.

Background. Invasive mycoses (IM) are one of the most severe infectious complications in oncohematology. The etiological structure of IM is a rather heterogeneous group of microorganisms and undergoes changes over time. Understanding the IM etiological structure is the basis for choosing an effective IM prevention and treatment strategy.
Aim. To conduct a systematic review with a meta-analysis of data on the IM etiological structure in patients of all ages receiving therapy for oncohematological diseases, including patients who underwent hematopoietic stem cell transplantation. The analytical hypothesis was the assumption of an increase in caused by rare pathogens IM proportion in the overall IM structure over the past few years. Clinical manifestations, affected organs, risk factors and outcomes were analyzed using the literature review method.
Materials and methods. A systematic search was carried out for publications with data on the IM species structure available for analysis until February 10, 2022 in 3 databases (PubMed (Medline), Embase and eLibrary.ru). All IM were divided into 11 groups. The IM species structure was constructed in several patient subgroups in 2 time ranges – in studies before 2010 and after 2010, and they were compared. Results from individual studies were pooled by metaanalysis. Data from selected publications were reviewed to analyze the IM clinical manifestations, risk factors for their development and outcomes.
Results. Thirty-four publications were selected using a systematic search. The meta-analysis included 43 cohorts of patients with 2771 samples of IM pathogens. The time period up to 2010 included 16 cohorts with a total number of IM pathogens of 1158 samples; in the time interval after 2010 – 27 cohorts with a total number of IM pathogens of 1613 samples. Analysis of total group showed that the proportion of rare IM among all patients increased from 29 to 39 %. In the subgroup of patients with oncohematological diseases, it increased from 28 to 33 %. For total group of patients, the in‑ crease in rare IM proportion is due to an increase in rare yeasts (from 3.0 to 4.1 %) and a significant increase in the proportion of unidentified species (from 3.2 to 19.8 %). In children, the frequency of rare IM increased from 26 to 28 % among all nosologies. For total children group, the increase in rare IM proportion is due to an increase in mucormycosis (from 1.3 to 1.6 %), rare yeasts (from 4.7 to 7.9 %) and unidentified species (from 4.5 to 12.2 %). In total adult patients group, the frequency of rare IM increased from 24 to 35 %, in adult patients with oncohematological diseases – from 23 to 40 %. For total adult patients group, the increase in rare IM proportion is due to an increase in cryptococcosis (from 1.3 to 2.4 %), hyalohyphomycosis (from 3.4 to 4.8 %), rare yeast (from 1.6 to 1.9 %) and unidentified species (from 1.9 to 16.6 %); for a group of patients with oncohematological diseases – an increase in cryptococcosis (from 1.3 to 2.1 %), rare yeast (from 1.6 to 2.6 %) and unidentified species (from 1.9 to 23.1 %). There is no specific clinical manifestations characteristic of IM, the symptoms are associated with the affected organ. Febrile fever is the only IM systemic clinical manifestation, independent of localization. The lungs were the most common IM localization. The main IM risk factors are prolonged blood cell deficiency, uncontrolled underlying disease, concomitant conditions: comorbidity, diabetes mellitus, mucositis, graft-versus-host disease, infections caused by other pathogens, and a history of IM. IM increases the risk of death, attributable mortality is variable and ranged from 13 to 72 %. The most common cause of death in oncohematological patients with IM is the progression of the underlying disease, in patients after hematopoietic stem cell transplantation – graft-versus-host disease, cardiovascular complications.
Conclusion. In IM structure in oncohematological patients and hematopoietic stem cell transplant recipients, the proportion of rare IM increased markedly, mainly due to an increase in their proportion in adult patients with oncohematological diseases. The increase in rare IM proportion is mainly due to the increase in unidentified species, hyalohyphomycosis, rare yeast and cryptococcosis. Clinical manifestations are due to the localization, the main of which is the lungs. The development of IM increases the risk of death, but attributable mortality is about 50 %.

Immunotherapy is a promising method in the treatment of cancer. PD-1 (programmed cell death protein 1) receptor and its ligand, which contribute to the reactivation of T-cells exerting their cytotoxic function against the tumor, are one of the targets of antitumor drugs. The effectiveness of immune checkpoint inhibitors has been demonstrated in the treatment of melanoma and non-small cell lung cancer. The spectrum of side effects of antitumor immune drugs differs from the classical ones observed in the cytostatics treatment. Immune-mediated adverse events can affect multiple organs, including skin, gastrointestinal tract, endocrine and nervous systems, and lungs. Pneumonitis is a potentially life-threatening complication and often requires immediate administration of corticosteroids.
This article presents the case of a patient with relapsed Burkitt lymphoma treated with nivolumab and R-ICE (rituximab, ifosfamide etoposide, carboplatin) scheme. The therapy was effective, but complicated by immune-mediated pneumonitis. Corticosteroids administration resolved this complication and anti-cancer treatment was completed. The following nivolumab administrations were free of side effects.

The use of colony-stimulating factors became an autonomous approach in complex supportive care of blood tumors. By indications of granulocyte colony-stimulating factor (G-CSF) it is possible to reduce of neutropenic period, perform an optimal timing of therapy, decrease a number of infection complications. The development and active use of a new G-CSF drug formulation – pegfilgrastim do not decrease the duration of neutropenic period significantly, but reduced the frequency of drug administration, period of hospitalization and a probability of “ineffective” hematopoietic stem cell mobilization.
In the current issue it is presented the results of modern studies, which demonstrate advantages of PEG-G-CSF in contrast to G-CSF, algorithm for febrile neutropenia risk assessment, the questions for G-CSF administrations in patients with blood tumors.

Since the middle of the last century, medical communities around the world have begun to attach great importance to the study of adherence to treatment in patients with diseases characterized by long-term and complex therapy, many complications and a potentially high risk of death. Treatment adherence is the single most important modifiable factor compromising treatment outcomes. Poor adherence to treatment remains a worldwide problem regardless of the racial and socio-economic characteristics of the regions. In our review article, we reviewed the relevance of the terms, the history of their occurrence, methods of adherence assessing, and also presented a literary review of studies aimed at adherence to therapy in patients with blood system diseases and recipients of allogeneic organs and tissues.