Polycythemia vera is a disease known since ancient times, however, until recent decades, diagnosis was carried out by exclusion, and therapy was symptomatic. The discovery of the pathogenetic role of mutations in the Janus kinase II gene has led to the possibility of establishing a diagnosis based not only on morphology, but also on genetic verification and to the development of directed targeted therapy, which is much more effective than previously used methods. The introduction of molecular genetic screening led to the need for a differential diagnosis with familial erythrocytosis, and the lessons of the coronavirus pandemic revealed the presence in the population of a significant proportion of patients with erythrocytosis due to the carriage of gene polymorphisms associated with familial hemochromatosis. The article presents our own personalized algorithms for the diagnosis and treatment of polycythemia vera and the results of their use, demonstrating the possibility of a two-fold reduction in the incidence of thrombosis and an increase in overall survival.

The use of high-effective, multicomponent, risk-adopted chemoimmunotherapy schemes in children with Burkitt lymphoma reached advanced long-term progression-free survival over 90 % even for high risk patients. Unfortunately, conventional therapeutic strategy for relapsed/refractory disease is not accepted, and the effectiveness of carboplat‑in- and gemcitabine-containing regimens is unsatisfactory. Clinical experience of rituximab, ibrutinib and nivolumab in combination with polychemotherapy and own clinical case of successful relapsed Burkitt lymphoma treatment with targeted therapy and following autologous and allogeneic hematopoietic stem cell transplantation are presented. Proposed program could achieve a complete remission of Burkitt lymphoma, but short-term after allogeneic hematopoietic stem cell transplantation diagnosed T-cell precursor acute lymphoblastic leukemia became fatal for the patient.

Aim. To examine the role of very good partial response or better (VGPR+) as a surrogate predictor of progression-free survival (PFS) in multiple myeloma (MM) patients.

Materials and methods. A systematic literature review of MEDLINE database (2010–2023) and materials presented at hematology and cancer congresses (2020–2022) was performed to identify studies reporting median progressionfree survival (PFS) and the rate of very good partial response (VGPR+). The study used Spearman’s weighted correlation and linear regression methods to analyze the association between median PFS and VGPR+. A total of 34,443 patients were involved in 182 original studies that included real-world clinical practice data.

Results. Based on the number of patients or year of publication, the correlation between VGPR+ and median PFS was statistically significant (Spearman coefficient r = 0.61), but low. For refractory/recurrent MM (r = 0.69) and for monoclonal antibody therapy (r = 0.81), the correlation between VGPR+ and PFS was stronger. In addition to achieving VGPR+, the line of therapy and autologous stem cell transplantation also played an important role in determining PFS. Based on these factors, an increase of one percentage point in VGPR+ predicted a 0.21‑month increase in median PFS in the final adjusted linear regression model.

Conclusion. In this study, VGPR+ was found to predict PFS, making it a universal early point of reference for MM prognosis regardless of the treatment type.

Aim. Identify risk factors for the development of osteodestructive syndrome. To determine the relationship between the types of secreted monoclonal immunoglobulin (paraprotein) and the severity of osteodestructive syndrome in patients with paraproteinemic hemoblastoses (PH) and Waldenström’s macroglobulinemia (WM).

Materials and methods. A retrospective analysis of data from 116 patients with PH and WM was performed. 104 patients (89.6 %) were diagnosed with multiple myeloma. Less commonly observed were WM (in 8 patients – 6.9 %), plasma cell leukemia (in 2 patients – 1.8 %), solitary plasmacytoma and monoclonal gammopathy of unknown significance were diagnosed in one case (0.9 %) each. According to the severity of osteodestructive syndrome, all patients were divided into 4 groups. The first group (0) included patients who did not have osteodestructive changes in the bones. In patients of the second group, a mild degree (I) osteodestructive process was observed, and in patients from the third and fourth groups – moderate (II) and severe (III) degrees, respectively. All patients underwent protein electrophoresis followed by immunofixation to determine the type of paraprotein and its concentration in serum and urine.

Results. In the majority of patients, paraproteins were detected in the blood – Gκ (35.1 %), Gλ (24.6 %), Bence Jones protein λ-type (BJλ) (14.9 %); in urine – BJλ protein (14.9 %) and Bence Jones protein κ-type (BJκ) (28.1 %). Secretion of other types of paraproteins in the blood was less frequently detected – Aκ (9.6 %), Aλ (7.0 %), Mκ (3.5 %), Mλ (3.5 %), Dλ (2.6 %), BJκ (4.4 %). Osteodestructive syndrome of I and II severity was diagnosed in 43 (37.1 %) and 40 (34.5 %) patients, respectively; lytic destruction of III degree was less frequently detected in 20 (17.2 %) patients, in 13 (11.2 %) patients osteodestruction was not detected (degree 0). It was noted that a higher degree of destruction (II, III) was observed in patients with multiple myeloma occurring with paraproteinemia Dλ and BJλ in the blood, as well as hypercalcemia. Osteodestructive syndrome of the lowest degree (0, I) was diagnosed in patients with the secretion of monoclonal proteins Ak and Mλ. There was no statistically significant relationship between the type of secretion of paraproteins Gκ, Gλ, Aλ, Mκ, BJκ in the blood, as well as proteins BJκ and BJλ in the urine and the severity of the osteodestructive process.

Conclusion. The results obtained in the study make it possible to identify risk groups, and parameters such as the type of paraprotein, the concentration of calcium in the blood serum can be considered as prognostic factors when assessing the severity of osteodestructive syndrome in patients with PH and WM.

This work was carried out in real clinical practice. Five clinical observations of anemia caused by vitamin B₁₂ deficiency are presented, which demonstrate the difficulties of differential diagnosis. Differential diagnosis of B₁₂‑deficiency anemia is carried out with folate deficiency anemia, hemolytic anemia, myelodysplastic syndrome, acute leukemia – erythromyelosis, aplastic anemia, myelocarcinomatosis, anemia due to copper deficiency. The relevance of the clinical problem is determined by the fact that B₁₂‑deficiency anemia is one of the common anemias, the frequency of its detection varies in different age groups: after 60 years, vitamin B₁₂ deficiency is found in one in 50 people, after 70 years – in every 15th. Currently, an increasingly common cause of megaloblastic anemia is vitamin B₁₂ deficiency, which occurs while taking certain medications. Vitamin deficiency leads to a wide range of various disorders, primarily the occurrence of neurological manifestations, while there is insufficient awareness of clinicians about causes of its occurrence, nonspecific manifestations, diagnostic methods and effective therapy.

Background. Paroxysmal nocturnal hemoglobinuria is a rare clonal disease of the hematopoietic system, with the key manifestations of hemolytic anemia, a high thrombosis rate, and bone marrow failure. Despite the high efficacy of C5‑inhibitors in intravascular hemolysis cessation, a significant proportion of patients remain anemic. Causes of a sub‑optimal response may include C3‑mediated extravascular (intracellular) hemolysis, residual intravascular hemolysis, or bone marrow failure.

Aim. To analyze the results of pathogenetic therapy in patients with paroxysmal nocturnal hemoglobinuria.

Materials and methods. The study included 55 patients with paroxysmal nocturnal hemoglobinuria receiving complement C5 inhibitors for at least 6 months. Results. Suboptimal hematological response was observed in 31/55 (56 %) patients. The most common cause of anemia in the partial response group was C3‑mediated extravascular hemolysis in 8/10 (80 %), while bone marrow failure predominated (57 %) in the minor response group.

Conclusion. The study showed a high frequency of suboptimal response to pathogenetic therapy and necessity of ac‑
curate determination of leading cause of persistent anemia in order to modify therapy or switch to other drugs.

Background. According to WHO guidelines, one of the criteria for diagnosis of polycythemia vera is the presence of somatic mutations in exon 12 of the JAK2 gene, but to date there is no universally accepted simple method to analyze these mutations. We have previously proposed two methods for screening such mutations based on heteroduplex and HRM (High Resolution Melt) assays, which are relatively cheap and fast compared to sequencing.

Aim. To analyze the sensitivity of these screening methods.

Materials and methods. The study used cloned DNA samples from 6 patients with various mutations in exon 12 of the JAK2 gene that we had previously identified, as well as a clone of the corresponding wild-type DNA segment. Dilution of the cloned mutant samples with wild-type clones was performed to obtain samples with different levels of allele burden: 100, 50, 25, 12.5, 6.25, 3.13, 1.56 and 0.78 %. Heteroduplex analysis followed by PAGE (polyacrylamide gel) and HRM analysis was then performed with the diluted samples.

Results. The sensitivity threshold of the heteroduplex analysis was found to be between 3.13–6.25 % allele burdens depending on the specific mutation, the sensitivity threshold of the HRM assay was 6.25–12.5 % similarly.

Conclusion. Our proposed methods of heteroduplex analysis followed by PAGE and HRM-analysis for the detection of polycythemia vera-specific mutations in exon 12 of the JAK2 gene allow increasing the efficiency of using different types of sequencing and can be used as simpler and less expensive methods of preliminary screening of these mutations.

Invasive fungal infections (IFIs) are a serious threat to patients with hematological diseases. These infections are characterized by high mortality and lead to significant financial costs for treatment. The most common pathogens of IFIs are Aspergillus spp. and Candida spp., but in recent years, cases of infections caused by rare pathogens have become more frequent. Diagnosis of IFIs and choice of treatment remain challenging due to the nonspecificity of symptoms and the diversity of clinical cases. In this regard, the problem of start time and choice of antifungal therapy remains of current interest. This review briefly describes diagnostic criteria, challenges associated with IFIs diagnosing, provides evidence for empiric and preventive strategies as two early treatment approaches, and examines the impact of therapy initiation on patient outcomes. Treatment of IFIs in hematologic patients should be individualized. At the same time, early administration of therapy with broad-spectrum drugs for febrile neutropenia and parallel diagnostic measures can improve treatment outcomes. There is a lack of current data on the benefits of specific treatment strategies, highlighting the need for further research.

Treatment intensification of acute lymphoblastic leukemia in children with L-asparaginase (L-ASP) improves therapy effectiveness and shows high survival rates. The unique biological properties of this enzyme make it possible to suppress tumor blasts proliferation by reducing blood asparagine concentration. L-ASP use is limited by toxicity and hypersensitivity reactions observed in 75 % of cases. Although most complications during L-ASP therapy are mild/moderate and are manageable with adequate accompanying therapy, the development of severe side effects leads to forced withdrawal of L-ASP, which significantly reduces the likelihood of a favorable outcome in children with acute lymphoblastic leukemia. One of the most severe toxicity manifestations is the development of asparaginase-associated pancreatitis. It worsens the prognosis and may cause patients’ death. This article presents both current data about asparaginase-associated pancreatitis and treatment experience of this complication at the Research Institute of Pediatric Oncology and Hematology of the N. N. Blokhin National Research Center of Oncology.