Introduction. The R-NHL-BFM-90 protocol has been successfully used for the treatment of Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL) in children and adolescents, as well as adult T-cell lymphomas. The protocol was modified for the treatment of adult patients with de novo nodal DLBCL.

Aim: to evaluate the efficacy and toxicity of the R-mNHL-BFM-90 and R-DA-EPOCH-21 protocols in adult patients with de novo nodal DLBCL with 2 or more signs of poor prognosis, as well as to determine the role of auto-HSCT in the consolidation of remission.

Materials and methods. From 2015 to 2021, 164 patients were evaluated for randomization. The study included 140 patients from 13 Russian medical centers. 89 (76 %) patients with de novo nodal DLBCL: R-DAEPOCH-21 20 (22.5 %) patients; R-DAEPOCH-21 + auto-HSCT 21 (23.5 %) patients; R-mNHL-BFM-90 20 (22.5 %) patients; R-mNHL-BFM-90 performed + auto-HSCT 28 (31.5 %) patients. In the high-intermediate and high-risk group, there were 12 (29.3 %) and 29 (70.7 %) patients on the R-DA-EPOCH-21 + auto-HSCT protocol and 15 (31.2 %) and 32 (66.7 %) on the R-mNHL-BFM-90 protocol + auto-HSCT, respectively.

Results. The R-mNHL-BFM-90 protocol proved to be more effective. Complete remission in the high-risk group was achieved in 30 (93.7 %) patients versus 18 (62.0 %), there was no progression versus 3 (10.3 %) patients treated according to R-DA-EPOCH-21 (p = 0.0167). The five-year overall and event-free survival in the high-risk group was 97 % vs. 75 % (p = 0.01) and 97 % vs. 72 % (p = 0.0026), respectively. In the intermediate risk group, the results of therapy did not differ. The toxicity of the R-mNHL-BFM-90 protocol exceeded the toxicity of R-DA-EPOCH-21 only in neutropenic fever (p = 0.04) and grade 3–4 thrombocytopenia (p = 0.0009).

Conclusion. The R-mNHL-BFM-90 protocol is effective for the treatment of patients with nodal de novo DLBCL diffuse large B-cell lymphoma of high-risk adults; its toxicity is acceptable. However, on the R-DA-EPOCH-21 therapy, the results of therapy are unsatisfactory. The R-DA-EPOCH-21 protocol with auto-HSCT was more effective than without auto-HSCT, however, due to the small number of patients, the results were unpresentative. The results of therapy according R-mNHL-BFM-90 protocol with auto-HSCT and without auto-HSCT were not differ.

Introduction. Perianal infection (PI) in patients with hematological malignancies is characterized by a wide spectrum of pathogens and a variety of clinical manifestations and mechanisms of development of the infectious process.

Aim: to study the pathogenetic mechanisms of PI development in patients with hematological malignancies and to develop prevention tactics.

Materials and methods. The prospective study included 132 patients with hematological malignancies who had episodes of PI. The infectious process in the pararectal fi ber was registered based on the data of clinical examination or magnetic resonance imaging. Sources of infection and microbiologic results were studied.

Results: Two main mechanisms of PI development were revealed, the frequency of which was statistically significantly different depending on the presence of neutropenia (p < 0.0001, odds ratio (OR) = 24.42 (confidence interval (CI) 95% [9.82–60.74]). In PI episodes that developed against the background of neutropenia, the predominant mechanism of infection was the penetration of microorganisms through broken tissue barriers (75 %): anal fissures were the entry gate of infection in 62.9 % of episodes; perianal ulcers and skin erosions — in 12.1 %. The alternative route of infection (cryptogladular mechanism) was registered in the majority of patients without neutropenia (66.7 %) and was represented by the involvement of crypts of the anal canal (28.6 %) or the presence of pararectal fistulas (38.1 %). Clinical manifestations of PI were associated with leukocyte count (p < 0.0001) and mechanism of infection (p < 0.0001). The median leukocyte count in patients with abscesses (2.12×10⁹ /L) was statistically significantly higher than in infiltrates (0.57×10⁹ /L) and necrosis (0.74×10⁹ /L). The main source of infection in infiltrates was anal fissures (70.4 %), while in abscesses the main sources of infection were crypts of the anal canal (39 %) and pararectal fistulas (36 %). The main causative agents of PI were Gram-negative bacteria (Escherichia coli (43 %), Klebsiella spp. (15 %), Pseudomonas aeruginosa (4.4 %)), and Enterococci (12.5 %). P. aeruginosa was isolated more often in necrosis (22 %) than in other clinical forms of PI (3–5 %) (p = 0.0033), while the frequency of detection of other bacteria was independent of the clinical manifestations of PI. PI was a microbiologically proven source of sepsis in 9.5 % of PI episodes. The probability of PI-associated bloodstream infections was highest at 5 days and was significantly higher in patients with neutropenia (10 % vs 2 %) (p = 0.0044).

Conclusion: Different mechanisms of pararectal cell infection should be taken into account when forming a strategy for the prevention of PI.

Introduction. Hemophagocytic syndrome (HPS) is a reaction of severe, excessive, but ineffective inflammation. HPS is divided into primary or as a complication of a different causes — secondary HPS (sHPS).

Aim: to analyze the effi cacy of different treatments in sHPS patients.

Materials and methods. For the retrospective analysis, the medical documentation of patients who were treated in the period from June 2009 to January 2023 was used. The H-Score and HLH-2004 criteria were used to verify sHPS. The results of clinical blood analysis and biochemical tests are presented. The survival was analyzed within two weeks after the verification of sHPS. The main treatment options for sHPS were etoposide, glucocorticosteroids (GCSs), anticancer therapy and intravenous immunoglobulin.

Results. The study included data from 130 patients, median age 56 years (18–90); 70 females and 60 males with sHPS. All patients received treatment with a drug change in cases of inefficiency: a total of 186 episodes. A stable response was achieved in 74 (56.9 %) patients. The median survival in patients without a response was 2 days. If the therapy was effective, the median survival was not reached. Positive dynamics were observed during the first day after the start of effective treatment, however, a few patients had transient worsening of some markers. The main factor in the negative prognosis was the degree of multiple organ failure during sHPS verification. In the group of patients with autoimmune diseases, GCSs were the most effective, with a response reached in 75 % of cases. For patients with resistance, as well as in patients with Epstein—Barr virus infection and blood malignancy, etoposide proved to be effective in 65.7 % of cases.

Conclusion. sHPS was accompanied by an increase in pancytopenia, cytolytic, cholestatic syndromes, hypocoagulation, azotemia, hypertriglyceridemia and excessive hyperferritinemia. After the initiation of effective therapy, persistent clinical and laboratory responses developed during the first day. Therapy by GCSs was effective in most patients with autoimmune diseases associated with sHPS. With other forms of sHPS in the studied group, etoposide had the most pronounced effect.

Introduction. A decrease in bone mineral density (BMD), the development of osteopenia and osteoporosis is observed in patients with chronic lymphocytic leukemia (CLL). Patients with CLL are at a higher risk of developing fractures due to osteoporosis compared to healthy age-matched individuals. The pathogenesis of the osteodestructive process in CLL has been poorly studied and may be associated with excessive generation of reactive oxygen species and/or inhibition of antioxidant defense.

Aim: to investigate the relationship between indicators of oxidative stress in bone tissue and indicators of osteopenia in patients with CLL.

Materials and methods. The study included 48 male patients with CLL aged 50–70 years, divided into group 1 (n = 34) without signs of osteopenia and group 2 (n = 14) with signs of osteopenia based on osteodensitometry (T-score from –1.0 SD to –2.5 SD). BMD, T- and Z-scores were assessed in the lumbar spine, proximal femoral neck (PFC), and proximal femur. In the bone tissue homogenate, the content of products of oxidative modification of proteins (OMP) was determined spectrophotometrically in spontaneous and metal-catalyzed modes, reserve-adaptation potential, and general antioxidant status.

Results. Osteopenia was detected in 30 % of patients with CLL according to osteodensitometry in the neck of the proximal femur. In patients with CLL and osteopenia, signs of oxidative stress were observed in the bone tissue: early OMP products of a neutral and basic nature, late products of a neutral nature accumulated in the spontaneous detection mode; early and late OMP products of a neutral and basic nature accumulated in the induced mode; reserve-adaptive potential, the general antioxidant status decreased. Signs of osteopenia in the PFC in patients with CLL in the femoral neck increased as the content of early and late OMP products in the bone tissue increased in spontaneous and metal-induced detection modes, and the general antioxidant status in the bone tissue decreased.

Conclusion. Based on the data obtained, it is possible to modernize diagnostic criteria and therapeutic approaches.

Introduction. Replacement therapy with coagulation factor VIII concentrates remains the standard of care for patients with hemophilia A. In 2023, the drug Eytoplasm, the first modern plasma-derived coagulation factor VIII concentrate developed in the Russian Federation, was authorized for medical use in the Russian Federation.

Aim: to study the efficacy, safety, immunogenicity, and pharmacokinetic properties of Eytoplasm.

Methods. A multicenter, prospective, open-label clinical trial was conducted in 55 patients over 12 years of age with severe hemophilia A who had previously received treatment with coagulation factor VIII concentrates (at least 150 exposure days). All patients received the drug for prophylactic treatment 2–3 times a week; the treatment duration was 6 months (at least 50 exposure days). In addition, the drug was used to treat bleeding. Ten patients underwent 10 surgical interventions (2 major and 8 minor). Pharmacokinetic parameters were determined after the first administration of the drug to patients and after 6 months of therapy.

Results. Eytoplasm pharmacokinetics properties are comparable with other plasma-derived coagulation factor VIII concentrates. No bleeding was recorded in 75.9% of patients. In 92.3 % of patients, a single administration of the drug was sufficient to stop an episode of bleeding. In all participants who completed the study, the residual activity of coagulation factor VIII 48–72 hours after drug administration was at least 1 %. Positive dynamics of APTT was showed during the study. Serious adverse events, allergic reactions, thrombotic and thromboembolic complications were absent in patients. In 3 patients, 4 adverse events associated with the use of the drug were registered: 2 cases of increased serum concentration of direct bilirubin and 2 cases of headache. An inhibitor to coagulation factor VIII was not detected in any patient. In none of the patients who did not have antibodies to parvovirus B19 before the first dose of Eytoplasm, antibodies were detected after 6 months of therapy.

Conclusion. Eytoplasm is an effective option for the prevention and treatment of bleeding, and during surgical interventions, including major ones, in patients with hemophilia A. The drug has a favorable safety profi le; its use was not associated with the formation of inhibitory antibodies, allergic reactions, thrombotic and thromboembolic complications.

Introduction. Despite the successes achieved in the treatment of lymphoblastic lymphomas from progenitor cells (LBL), an important task in improving survival rates in the group of patients with T-cell lymphoblastic lymphomas (T-LBL) remains. The group of special unfavorable prognosis consists of patients with relapses and refractory forms (r/r) of T-LBL.

Aim: to present a literature review on the use of targeted and immune drugs, as well as cellular and transplant methods in the treatment of r/r T-LBL.

Main findings. Modern clinical onco-hematology has a broad spectrum of methods for the treatment of r/r T-LBL, including intensive chemotherapy, targeted, transplant and CAR-T technologies, but even a combination of these methods, currently, does not make it possible to achieve optimistic results in this prognostically unfavorable group of patients. It is possible that the creation of targeted drugs focused on signaling pathways (NOTCH, PI3K/ACT/mTOR, JAK/STAT and MAPK) with modern therapeutic potential could improve patient survival rates.

Introduction. Patients with relapsed/refractory (r/r) Ph-positive acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options. New promising immunotherapies using CAR T cells or monoclonal antibodies (blinatumomab, inotuzumab/ozogamicin) in combination with tyrosine kinase inhibitors are being used for this group of patients. However, long-term results have not been studied when relapse or refractoriness develops after the use of one of these methods.

Aim: to present a clinical observation of the use of anti-CD19 CAR T therapy after blinatumomab therapy in a patient with a relapsed course of Ph-positive acute lymphoblastic leukemia.

Main findings. A 28-year-old patient was first diagnosed with Ph-positive B-ALL (transcript p210) in 2014. In the 1st line of treatment he was treated with therapy according to the protocol ‘ALL-2009’ with imatinib and allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, 2 months later the first molecular relapse was detected, and imatinib was replaced by dasatinib. In November 2016, a second relapse was diagnosed. In 2017, a third relapse with testicular involvement and T315I mutation was diagnosed, and therapy with ponatinib was initiated. In 2022, a 4th medullary relapse developed, and therapy with blinatumomab (5 courses) in combination with ponatinib was performed. After the 5th course of therapy, the appearance of leukaemides was noted, and asciminib was added to the therapy. However, no clinical effect was noted. The patient was treated with anti-CD19 CAR T therapy. A complete response to CAR T-cell therapy was confirmed on day 28 after CAR T administration. Further follow-up, over the course of one year, demonstrated stable clinical response and persistence of CD3-positive CAR T-cells. This case report of anti-CD19 CAR T cell therapy in a patient with CD19-positive combined relapse with massive extramedullary component after blinatumomab therapy demonstrated long-term efficacy with a 1-year follow-up.

Introduction. Extracorporeal photopheresis (ECP) is an attractive method of treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation due to the lack of systemic immunosuppression. However, the clinical use of ECP is often limited by the need for leukapheresis. There are modifications of ECP without the use of leukapheresis, in particular low-volume ECP.

Aim: to analyze the use of lv-ECP for the treatment of patients with acute and chronic GvHD.

Patients and methods. The results of treatment of 9 cases of acute GVHD and 15 cases of chronic GVHD using the lv-ECP from April 2021 to March 2024 are presented. The cellular product was obtained by effusion of 15-30 ml of whole blood followed by photochemical treatment. The processed autologous cell product was administered to the patient.

Results. The overall response in patients with acute GVHD was 44%, organ-specific response for skin lesions was 56 %, and for gastrointestinal lesions, 40%. In the treatment of chronic GvHD, the overall response was 73.3 %; the effectiveness of therapy for skin lesions was 71 %; for gastrointestinal lesions 67 %; for lung damage 67 %; for eye damage 100 %, for liver damage 100 %.

Conclusion. lv-ECP has shown promising efficacy results in the treatment of acute and chronic GvHD. lv-ECP is an attractive alternative to standard ECP when leukapheresis is not possible.