Background. Current chemotherapy protocols for T-cell acute lymphoblastic leukemia (T-ALL) allow achieving a 5-year overall survival of 60–90 %, but relapsed and refractory forms remain incurable situations.

Aim. To determine the significance of immunophenotypic, cytogenetic and molecular markers in adult T-ALL patients receiving therapy according to the ALL-2016 protocol.

Materials and methods. From December 2016 to June 2022, 113 patients with primary T-ALL were included in the study. Cytogenetic study was performed in 104 (92 %) patients; anomalies in the IKZF1 and NOTCH1 genes were investigated in 43 (38 %) patients.

Results. The worst prognosis was in patients with ETP and near-ETP variants of T-ALL (3-year disease-free survival was 54 % in ETP group, 33 % in near-ETP group vs TI/II – 79 %, TIII – 89 %, TIV – 75 %). In early T-ALL variants, abnormal karyotype was most common (ETP – 80.7 %, near-ETP – 60 %). Aberrations in NOTCH1 gene were found in 53 % of cases (in 23 out of 43 patients), and no mutations were found in IKZF1 gene in our study. In the group with no NOTCH1 abnormalities, the overall survival was significantly worse than in the group with abnormalities (NOTCH1– – 52 % vs NOTCH1+ –81 %; p = 0.05).

Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m²) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.

Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.

Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.

Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.

Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.

Background. Vascular endothelial growth factor A (VEGFA) is one of the most important factors for regulation of hematopoietic stem cells differentiation. It is involved in leukemogenesis and central nervous system (CNS) damage in acute leukemia. According to the literature, the VEGFA production by blast cells is increased, but the values of serum concentration and the associations with CNS involvement are contradictory.

Aim. evaluate the VEGFA, VEGFR1, VEGFR2 concentration in serum and cerebrospinal fluid of patient with different types of acute leukemia in disease onset and during treatment.

Materials and methods. The concentration of VEGFA in serum and cerebrospinal fluid was studied in 74 primary patients with acute leukemia. The comparison group consisted of 67 healthy donors. VEGFR1, VEGFR2 were studied in serum and cerebrospinal fluid in 34 patients at the onset of the disease. The comparison group consisted of 10 healthy donors. For the analysis, an enzyme immunoassay was used on a semi-automatic Personal Lab analyzer (Adaltis) and Affymetrix eBioscience human VEGF-A Platinum ELISA reagents.

Results. Serum VEGFA concentration was statistically significantly lower in acute leukemia patients than that of donors (median 149.78 and 432.19 pg/ml respectively; p <0.0001). Factor deficiency was significantly more pronounced in patients with blastemia (p <0.015). During antitumor therapy, there was a tendency to increase the amount of the factor in the blood serum. Serum concentration of soluble VEGFR2 was also lower in patients than that of donors (6949.9 and 8795.9 pg/ml respectively; p = 0.0026). For concentration of VEGFR1 such deviations were not found. The concentrations of VEGFR1 and VEGFR2 in serum were higher than in cerebrospinal fluid (p <0.0001), while VEGFR1 showed a positive correlation between serum and cerebrospinal fluid concentrations. the concentration of VEGFR1 in the cerebrospinal fluid was significantly lower in patients with B-lymphoblastic leukemia/lymphoma compared to other types of leukemia.

Conclusion. the concentration of VEGFA in serum decreases in patients with blastemia, this may indicate a lack of secretion and excessive consumption of the factor by blast cells with a decrease in the proportion of leukocytes that normally secrete the factor. In the cerebrospinal fluid, the concentrations of VEGFR1 and VEGFR2 are lower than in serum, with the lowest values being found in patients with B-lymphoblastic leukemia/lymphoma, but no relationship with the development of CNS involvement was found.

Rosai–Dorfman disease is the most frequent variant of non-Langerhans cell histiocytosis. Local forms can be resected or irradiated. If the process involves multiple organs, systemic chemotherapy can cure some patients. This article includes literature review and a case report of a 34-year-old patient with multifocal, multisystemic form of Rosai–Dorfman disease with bone and pleural involvement. The diagnosis was based on histological, immunohistochemical, and molecular studies of tumor tissue. Since November 2021, 6 courses of chemotherapy with cladribine and 8 infusions of zolendronic acid were carried out with achievement of durable remission. The tolerance was acceptable.

Background. Differentiation syndrome (DS) is a potentially fatal complication of therapy for acute promyelocytic leukemia (APL) with an incidence of up to 48 %. To date, no reliable DS risk factors have been found, with the exception of leukocytosis at the APL onset.

Aim. To determine the risk factors associated with DS in patients with APL during induction therapy with arsenic trioxide (ATO) and tretinoin (ATRA).

Materials and methods. The study included 39 patients with APL, 29 (74.4 %) of them were classified as low-risk according to ELN (European Leukemia Net), 10 (25.6 %) were classified as high-risk. At the disease onset, cytological and molecular (chimeric transcript PML::RARα, FLT3-ITD mutation) bone marrow studies were performed, the expression of 28 differentiation antigens by blood and bone marrow blast cells was determined (markers of early precursors, myeloid and lymphoid differentiation, cell adhesion molecules, chemokine receptors, integrins, selectin), body mass index (BMI) and the leukocytes number dynamics during induction course were assessed. All patients received ATRA and ATO therapy. Patients from the high-risk group at the onset received 1–3 injections of idarubicin (12 mg/m²) and dexamethasone (8–10 mg/m² 2 times a day) to prevent DS until leukocytosis reduced. In cases of DS, dexamethasone was prescribed at a dose of 10 mg/m² 2 times a day; in cases of severe DS, the induction course was interrupted.

Results. Of the 39 patients, 12 (30.8 %) were diagnosed with DS: 20 % of high-risk patients (2/10) and 34.5 % of low-risk patients (10/29). There was no statistically significant association of leukocytosis more than 10 × 10⁹ /L at onset, microgranular morphology of blast cells, bcr3-variant PML::RARα, FLT3-ITD mutation with DS. In multivariate analysis, the probability of DS was associated with BMI ≥30 kg/m² and mean fluorescence intensity of CD38 antigen by blast cells, regardless of risk group. based on the results of the ROC-analysis, the threshold value of mean CD38 fluorescence intensity was set at 25,000 cu, if exceeded, DS is highly likely to develop.

Conclusion. the high incidence of DS among low-risk patients is probably due to the lack of prophylactic glucocorticosteroids administration for the development of leukocytosis during ATRA and ATO therapy. BMI ≥30 kg/m² and mean CD38 fluorescence intensity more than 25,000 cu were identified as statistically significant DS risk factors.

Aim. To study the glomerular filtration rate (GFR) dynamics calculated by creatinine and cystatin C during induction immunochemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma in order to objectify the method for estimation.

Materials and methods. The open longitudinal study included 39 patients with newly diagnosed diffuse large B-cell lymphoma who received specialized treatment at the Oncohematology Department of National Medical Research Centre for Oncology (Rostov-on-Don) in 2021. Patients received induction immunochemotherapy according to the R-CHOP regimen (rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone) in combination with accompanying therapy (allopurinol 300 mg/day). Blood sampling was carried out at 0, 24, 48, 72, 120 hours and on 21^st day of the 1^st therapy cycle. Patients were divided into 2 groups depending on the GFR level, calculated by creatinine, before treatment: group A – 27 (69 %) patients with GFR >90 ml/min/1.73 m², group B – 12 (31 %) patients with GFR <90 ml/min/1.73 m².

Results. During the immunochemotherapy in patients with initially reduced GFR, a further decrease was observed with the restoration of the initial level by day 21 of therapy. When calculating GFR by cystatin C, in contrast to the calculation by creatinine, it revealed the dependence of GFR level on pathological process stage: GFR in group A patients with stages I–II is 20.4 % lower than in patients with stages III–IV, in group B – by 30.5 %. The use of the fisher test at GFR thresholds of 90 and 60 ml/min/1.73 m² revealed a greater advantage in establishing absolute GFR levels, especially in the range of 60 to 90 ml/min/1.73 m².

Conclusion. The data obtained confirm that the determination of GFR by cystatin C in patients with diffuse large B-cell lymphoma is a more sensitive method that objectively reflects the functional state of the kidneys, especially when values are within the “gray area” – from 90 to 60 ml/min/1.73 m².

Diffuse large B-cell lymphoma is the most common immunomorphological variant of lymphoma in adults. Extranodal lesions are observed in a third of patients at the disease onset. The organs most often involved are the gastrointestinal tract, testicles, bones, thyroid gland, and skin. Primary involvement of the nasal cavity and paranasal sinuses occur extremely rarely and cause diagnostic and therapeutic difficulties.

The article demonstrates a rare clinical case of newly diagnosed diffuse large B-cell lymphoma with sinonasal tract involvement. It took 6 months to verify the final diagnosis. At the moment, the induction stage of treatment for diffuse large B-cell lymphoma continues, the achieved complete metabolic response is maintained.

Nijmegen syndrome is a rare monogenic pathology with an autosomal recessive type of inheritance. The disease is manifested by congenital developmental anomalies and microcephaly, primary immunodeficiency, frequent recurrent viral and bacterial infections, retardation in physical and neuropsychic development. In the medical literature, 150 cases of the syndrome are described; pathology occurs more often among the Slavic population. Nijmegen syndrome belongs to a group of diseases with chromosomal instability. The pathogenetic feature of the syndrome is congenital immunodeficiency of the humoral (B-lymphocytes) and cellular (T-lymphocytes) components. According to statistics, 40 % of children with Nijmegen syndrome are diagnosed with malignant neoplasms. lymphoid tissue is more often affected (non-Hodgkin’s B and T-cell lymphomas, acute lymphoblastic leukemia), and the development of solid neoplasia is also possible. To diagnose Nijmegen syndrome, in addition to assessing the patient clinical status, it is necessary to conduct an extended immunological examination with the determination of immunoglobulins A, M, G and molecular genetic studies.

The article presents a clinical case of diagnosis and treatment of Nijmegen syndrome in childhood.

With the development of modern next generation sequencing based DNA diagnostic methods, it has become possible to study hereditary predisposition to oncohematological diseases. Germline variants (mutations) of RUNX1, CEBPA, GATA2, ANKRD26, DDX41, FANC- (Fanconi anemia), etc. genes, associated with the development of hereditary hematological malignancies, have been identified. Timely diagnosis of such diseases will allow for medical genetic counseling and testing of the patient’s relatives to identify or exclude the risk of developing the disease, select a donor for the patient (it is undesirable to use a mutation carrier relative as a donor), and personalize the choice of chemotherapy regimens (for example, patients with Fanconi anemia may experience increased sensitivity to chemotherapy). The aim of this review is to present a modern view of the genetic predisposition to the development of hematological malignancies.

Treatment of immunocompromised patients with novel coronavirus infection (COVID-19) presents significant challenges. Currently, there are no unified approaches to the treatment of persistent COVID-19 in hematological malignancies. There is a need to develop recommendations for the management of such patients, chemotherapy protocols, as well as therapy for COVID-19 in case of SARS-CoV-2 virus persistence. Doctors are faced with cases of virus persistence, clinical manifestations during a long course of the infectious process and are not provided with methodological recommendations for patient supervision. As scientific data on the persistent COVID-19 course in patients with lymphoproliferative diseases accumulates, it is planned to create recommendations for the treatment of COVID-19 for patients in this group. This article describes a clinical case of persistent COVID-19 course in a comorbid patient with primary central nervous system large B-cell lymphoma during chemotherapy.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and decreased platelet production. The formation of antibodies to platelet and megakaryocyte glycoproteins plays a major role in the pathophysiology of ITP. All treatment strategies for ITP attempt to increase platelet count and reduce the risk of bleeding complications. Corticosteroids remain the most commonly used first-line therapy for ITP, but their long-term use is limited due to the development of severe complications. Today the new treatment methods including the use of thrombopoietin receptor agonists (TPO-RA) romiplostim, eltrombopag and avatrombopag with a number of advantages over standard therapy are of great interest. These drugs are recommended for use in the second-line therapy and show high efficacy in patients with ITP, particularly in real clinical practice. In most cases TPO-RA provide stable and long-term remission of the disease, allowing you to reduce or discontinue the use of glucocorticosteroids and avoid splenectomy. Many studies of the mechanism of action, efficacy and toxicity of TPO-RA have been performed. the research results significantly expand our knowledge about these agents. This review provides comparative data of the TPO-RA safety and the main aspects of their clinical use. The features of the new drug avatrombopag, recently approved for use in the Russian federation, are described. the overview presents the advantages and limitations of each drug, possible adverse events and methods for their control.

Glucocorticosteroids are highly effective anti-inflammatory and immunosuppressive agents. The drugs were introduced into therapeutic practice from the mid-20^th century and are still widely used in the treatment of various diseases. They are an integral part of the treatment of patients with hematological malignancies. One of the clinically significant complications of glucocorticosteroid therapy is steroid-induced carbohydrate metabolism disorders. Diabetes mellitus is one of the main risk factors for the development of cardiovascular diseases, which are the main non-oncological cause of death in the population and a significant treatment complication in patients with malignant neoplasms. Early detection of the disease and improved treatment efficiency increase the survival rate of patients with various types of neoplasms. It is also important to pay attention to quality of life improving in cancer patients after treatment.

The aim of this review is to analyze the pathogenesis features, as well as predictors of early detection and prevention of possible complications of persistent hyperglycemia in patients with hematological malignancies.

Background. Anemia represents one of the most frequent complications in inflammatory bowel disease and severely impairs the quality of life of affected patients. The etiology of anemia in inflammatory bowel disease patients can be multifactorial, often involving a combination of iron deficiency anemia and anemia of chronic disease. The choice of therapy, focused on the leading cause of anemia, allows for individualized therapy, minimizing the risk of side effects and the cost of therapy.

Aim. A comparative analysis of blood parameters before and after treatment was performed.

Materials and methods. For 5 years, 47 patients (15 women, 32 men) with inflammatory bowel disease with a median age of 48 years (from 28 to 65 years) were studied. Two groups were formed: patients with iron deficiency anemia and patients with anemia of chronic disease. Patients with combination of iron deficiency anemia and anemia of chronic disease D (n = 21) were not included. A division was also made according to the type of treatment performed.

Results. In the iron deficiency anemia group, a statistically significant increase in hemoglobin level was revealed as a result of the use of intravenous iron. During therapy with oral iron and B vitamin therapy, as well as therapy aimed only at correcting gastrointestinal tract pathology, no reliable dynamics of the studied parameters was observed. In the anemia of chronic disease group, there were no significant changes in red blood cell parameters with any of the treatment options (p >0.05).

Conclusion. The effectiveness of various therapeutic approaches to correct anemia is controversial. Further follow-up and an increase in the sample size are needed, which will help individualize therapy and improve the patients’ quality of life.

L-asparaginase is one of the most effective drugs in pediatric and adult acute lymphoblastic leukemia treatment. But drug side effects are an important problem. pancreatitis and pancreatic necrosis are not common (2–18 %) complication, but high chance of severe disease with fatal outcome make to bring in careful attention of pediatric oncologists-hematologists, surgeons, intensivists, radiologists. Recognizing multidisciplinary importance of this problem, at June 21^st, 2023 at Morozov Children’s Clinical hospital a Round table on pancreatitis/pancreatic necrosis after L-asparaginase use was organized. This article presents expert recommendations from federal and regional clinics in diagnosis and treatment of such severe complication.