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.

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.

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.

Analysis of treatment results of 165 primary adult patients with diffuse B large-cells lymphoma (DBLCL) treating in Moscow municipal clinics is presented. Study aimed on analysis of efficacy of various dose intensity chemotherapy schedule according to disease molecular genetics variants. 28 adolescents and young adults (median age — 21.7 years) have received treatment according to pediatric BFM-NHL 90m and BFM-NHL 2004M protocols, 46 (median age — 29.0 years) and 91 (median age — 59.5) adults according to courses CHOP and R-CHOP, respectively. It was not randomized study. Germinal and postgerminal variants DBLCL were determined using immunohistochemical technique for 58 (35%) patients with appropriate primary samples. For young patients with germinal DBLCL therapy superiority of intensive BFM-NHL 90m and B-NHL 2004M protocols in relation to postgerminal variants was revealed: 5-years event-free survival (EFS) was 1.0 ± 0.0 (n = 6) versus 0.44 ± 0.15 (n = 9), respectively (p 0.05). Data receiving proves expediency of treatment adolescents and young adults with DBCLC from germinal center cells according to intensity BFM-like protocols.

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.

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.

Treatment results in a group of patients with multiple myeloma (n=18) treated with melfalan (200 mg/m2) followed by autologous peripheral blood stem cell transplantation as a second-line therapy are presented. Thirteen patients received one course of high-dose chemotherapy (HDCT), 5 had 2 courses. Before HDCT all treated patients achieved a partial remission (15 patients after 3 courses VAD, 3 patients after 3 courses of VAD and 2 courses of velcade- doxorubicin- prednisolone). The median time to disease progression was 33.1 (range 26—40) months; that of overall survival was 55.4 (range 29— 40) months.

Neutropenia and associated infection, resulting in hospitalization and use of antibiotics, has a negative effect on chemotherapy. The need to reduce the dose of cytotoxic drugs during neutropenia leads to lower survival rates in patients with hematological malignancies and solid tumors. Since 1990s myelocytokines – proteins that accelerate neutrophil recovery after cytostatic chemotherapy and reduce the risk of infection – is widely used in the clinical practice. The use of these drugs can support the planned dose intensity of chemotherapy and improves the treatment efficacy. The disadvantages of these drugs include the need for their daily parenteral administration for 7–10 days. The development of long-acting forms (pegfilgrastim and lipegfilgrastim) has solved this problem. Self-regulating clearance of prolonged forms allowed to use them only once on a chemotherapy course. Results of pegfilgrastim administration in 25 patients with hematological malignancies (8 patients) and solid tumors (17 patients) included in our analysis. Prolonged preparation showed high efficacy in secondary prophylaxis of neutropenia and infection decreasing the risk by 82 %. The single administration of pegfilgrastim allowed safe dose intensity chemotherapy with shorter intervals between courses (AC-14) in 8 patients with breast cancer. Tolerability was good; cases of hyperleukocytosis have notbeen reported. Recently in Europe and the Russian Federation a new drug from prolonged myelocytokine group – lipegfilgrastim – has been registered. The results of two controlled trials in patients with breast cancer (n = 410) receiving doxorubicin/docetaxel showed high efficacy of the drug as the pegfilgrastim with comparable tolerability.

ITP is a rare chronic autoimmune disease with isolated platelets decrease and high risk of bleeding complications. Standard treatment (steroids, HD of immunoglobulin and splenectomy) are effective in 70–90 % of patients, but in 10 % of them platelet count is not increased. A new group of drugs — TPO receptor agonists — is able to help to these patients. Their high efficacy in chronic ITP has shown in several studies, but the experience of their application before surgery is limited. We used romiplostim in 3 patients with chronic refractory ITP before surgery (2 — splenectomy and 1 — resection of nasal tumor). Thefirst patient, 19 years old, received multiple steroids, immunoglobulins and rituximab courses without effect during the last year. Platelets count was 7–15  10 9/l and hematuria and steroid tibia necrosis were revealed. Splenectomy was decided to be done. Because of the risk of hemorrhagic complications patients received romiplostim (3 mkg/kg) during 4 weeks. Upon reaching platelet counts 240  10 9/l splenectomywas performed. A postoperative platelet count was 1200  10 9/l, 3 weeks later — 400  10 9/l. The second patient, 64 years old, with a3-year ITP history was admitted to the hospital for splenectomy, but the platelet count (5.7  10 9/l) and a hemorrhagic syndrome with a constant need for platelet transfusions despite high doses of steroids and immunoglobulin received, interfere with the safety of operations.Romiplostim was administered in increasing doses during 6 weeks to a maximum 10 mg/kg. Platelet count was 148  10 9/l and splenectomy was performed. Postoperative platelet count was 380  10 9/l, 3 weeks later — 120  10 9/l. The third patient, 22 years old, with a 15-year ITP history admitted with severe epistaxis. Nasal tumor was revealed. Patient was treated with immunoglobulins and steroids, and biopsy was attempt when platelet count increased to 50  10 9/l. This procedure ended with severe bleeding. Patient received 1 mg/kg of romiplostim and a week later platelet count was 250  10 9/l. Successfully tumor resection was done. No romiplostim side effects or thrombotic complications during postoperative period were found. The obtained data together with similar case reports of successful surgery after TPO-agonists administration allow considering romiplostim as an effective method of thrombocytopenia therapy before surgery in ITP patients.

Hodgkin’s lymphoma (HL) is highly sensitive to chemo- and radiotherapy. Long-term tumor-free survival in patients with early stages is close to 95–98 %. Therapy results in patients with advanced stages is worse that requires an intensification of treatment and creates the issuesof late toxicity prevention. These problems are especially relevant in young adults with a life expectancy of 40 years or more. Escalated BEACOPP protocol developed by the German study group allows to achieve cure the majority of patients with advanced-stage Hodgkin’s lymphoma, but this regime has significant toxicity. It causes infertility in almost all patients. BEACOPP-14 with comparable activity contains less cumulative doses of potentially gonadotoxic alkylating agents. Efficacy and toxicity of this regime has been analyzed in 29 patients with prognostically unfavorable stages of HL (m – 13, f – 16) received 8 courses BEACOPP-14 without a dose reduction of cytostatics. The median age of patients was 24 (20–35) years. With a median follow-up of 32.8 (4–66) months, event-free survival was 92.8 %, disease-free – 96.2 %, and overall survival – 95.2 %. Of the 16 women included in the study, the menstrual cycle was restored in 14 patients during 3–6 months. 2 patients were not evaluated because of switch to more intensive chemotherapy in the early stages of treatment. Of the remaining 14 patients pregnancy occurred in 3 (18.7 %), delivery – in 2, abortion – in 1. Delivery was term, children born healthy. Most of the patients according to the doctors’ recommendations protects and continues to avoid pregnancy for 2 years after treatment. The data indicate a potentially less reproductive damaging of BEACOPP-14 in females retaining high anti-tumor efficacy.

Central nervous system (CNS) involvement in advanced non-Hodgkin’s lymphoma (NHL) occurs in 5–29 % of cases. Primary CNS lymphoma (PLCNS) significantly less revealed: 1–2 % of lymphoma cases and 5 % of all malignant CNS diseases. Historically, PLCNS treated with radiotherapy, but the majority of patients had no long-term remission. Combined treatment (chemotherapy + radiation therap y) has been developed to improve radiotherapy efficacy. The research results, according to several authors, allowed to develop the bas is of modern medical approaches, which includes a combination of high-doses methotrexate and cytarabine with radiation therapy for remission consolidation. New drugs — temozolomide, topotecan and rituximab — in combination with conventional preparates have been studied. Treatment results of 11 patients with primary (8) or secondary (3) CNS lymphomas treated in Botkin Municipal Clinical Hospital was analyzed. In 9 from 11 (all with primary lesion) diffuse B-large cell lymphoma w as diagnosed (by immunohistochemistry). All primary patients received 3.5–5 g/m2 methotrexate and 2–4 doses 2 g/m2 cytarabine (except 2 patients); 3 patients in addition received ifosfamide, vincristine and etoposide under a pediatric protocol BFM-90. Subsequently , all patients received 46 Gy cranial irradiation. 75 % of pa tients achieved complete or partial remission. One patient died from infectious complication after 2nd chemotherapy course. 2 patients have early progression. Five patients are alive with follow-up from 6 months to 3.5 years and 4 of them remains in remission. Therapy with methotrexate + cytarabine was accompanied by III–IV grade neutropenia in the majority of patients, but its duration w as not great. The data obtained are consistent with results of modern treatment protocols PLCNS.

ITP is a rare chronic autoimmune disease with isolated platelets decrease and high risk of bleeding complications. Standard treatment (steroids, HD of immunoglobulin and splenectomy) are effective in 70–90 % of patients, but in 10 % of them platelet count is not increased. A new group of drugs — TPO receptor agonists — is able to help to these patients. Their high efficacy in chronic ITP has shown in several studies, but the experience of their application before surgery is limited. We used romiplostim in 3 patients with chronic refractory ITP before surgery (2 — splenectomy and 1 — resection of nasal tumor). The first patient, 19 years old, received multiple steroids, immunoglobulins and rituximab courses without effect during the last year. Platelets count was 7–15  10 9/l and hematuria and steroid tibia necrosis were revealed. Splenectomy was decided to be done. Because of the risk of hemorrhagic complications patients received romiplostim (3 mkg/kg) during 4 weeks. Upon reaching platelet counts 240  10 9/l splenectomy was performed. A postoperative platelet count was 1200  10 9/l, 3 weeks later — 400  10 9/l. The second patient, 64 years old, with a 3-year ITP history was admitted to the hospital for splenectomy, but the platelet count (5.7  10 9/l) and a hemorrhagic syndrome with a constant need for platelet transfusions despite high doses of steroids and immunoglobulin received, interfere with the safety of operations. Romiplostim was administered in increasing doses during 6 weeks to a maximum 10 mg/kg. Platelet count was 148  10 9/l and splenectomy was performed. Postoperative platelet count was 380  10 9/l, 3 weeks later — 120  10 9/l. The third patient, 22 years old, with a 15-year ITP history admitted with severe epistaxis. Nasal tumor was revealed. Patient was treated with immunoglobulins and steroids, and biopsy was attempt when platelet count increased to 50  10 9/l. This procedure ended with severe bleeding. Patient received 1 mg/kg of romiplostim and a week later platelet count was 250  10 9/l. Successfully tumor resection was done. No romiplostim side effects or thrombotic complications during postoperative period were found. The obtained data together with similar case reports of successful surgery after TPO-agonists administration allow considering romiplostim as an effective method of thrombocytopenia therapy before surgery in ITP patients.

Hodgkin’s lymphoma (HL) is highly sensitive to chemo- and radiotherapy. Long-term tumor-free survival in patients with early stages is close to 95–98 %. Therapy results in patients with advanced stages is worse that requires an intensification of treatment and creates the issues of late toxicity prevention. These problems are especially relevant in young adults with a life expectancy of 40 years or more. Escalated BEACOPP protocol developed by the German study group allows to achieve cure the majority of patients with advanced-stage Hodgkin’s lymphoma, but this regime has significant toxicity. It causes infertility in almost all patients. BEACOPP-14 with comparable activity contains less cumulative doses of potentially gonadotoxic alkylating agents. Efficacy and toxicity of this regime has been analyzed in 29 patients with prognostically unfavorable stages of HL (m – 13, f – 16) received 8 courses BEACOPP-14 without a dose reduction of cytostatics. The median age of patients was 24 (20–35) years. With a median follow-up of 32.8 (4–66) months, event-free survival was 92.8 %, disease-free – 96.2 %, and overall survival – 95.2 %. Of the 16 women included in the study, the menstrual cycle was restored in 14 patients during 3–6 months. 2 patients were not evaluated because of switch to more intensive chemotherapy in the early stages of treatment. Of the remaining 14 patients pregnancy occurred in 3 (18.7 %), delivery – in 2, abortion – in 1. Delivery was term, children born healthy. Most of the patients according to the doctors’ recommendations protects and continues to avoid pregnancy for 2 years after treatment. The data indicate a potentially less reproductive damaging of BEACOPP-14 in females retaining high anti-tumor efficacy.

Central nervous system (CNS) involvement in advanced non-Hodgkin’s lymphoma (NHL) occurs in 5–29 % of cases. Primary CNS lymphoma (PLCNS) significantly less revealed: 1–2 % of lymphoma cases and 5 % of all malignant CNS diseases. Historically, PLCNS treated with radiotherapy, but the majority of patients had no long-term remission. Combined treatment (chemotherapy + radiation therap y) has been developed to improve radiotherapy efficacy. The research results, according to several authors, allowed to develop the bas is of modern medical approaches, which includes a combination of high-doses methotrexate and cytarabine with radiation therapy for remission consolidation. New drugs — temozolomide, topotecan and rituximab — in combination with conventional preparates have been studied. Treatment results of 11 patients with primary (8) or secondary (3) CNS lymphomas treated in Botkin Municipal Clinical Hospital was analyzed. In 9 from 11 (all with primary lesion) diffuse B-large cell lymphoma w as diagnosed (by immunohistochemistry). All primary patients received 3.5–5 g/m2 methotrexate and 2–4 doses 2 g/m2 cytarabine (except 2 patients); 3 patients in addition received ifosfamide, vincristine and etoposide under a pediatric protocol BFM-90. Subsequently , all patients received 46 Gy cranial irradiation. 75 % of pa tients achieved complete or partial remission. One patient died from infectious complication after 2nd chemotherapy course. 2 patients have early progression. Five patients are alive with follow-up from 6 months to 3.5 years and 4 of them remains in remission. Therapy with methotrexate + cytarabine was accompanied by III–IV grade neutropenia in the majority of patients, but its duration w as not great. The data obtained are consistent with results of modern treatment protocols PLCNS.

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82–88% of all NHLs. The proportions of chronic lymphatic leukemia (4–6%), mantle cell lymphoma (MCL, 3–5%), and plasmacytoma (2–4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6–7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3–5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

Treatment results in a group of patients with multiple myeloma (n =18) treated with melfalan (200 mg/m2) followed by autologous peripheral blood stem cell transplantation as a second-line therapy are presented. Thirteen patients received one course of high-dose chemotherapy (HDCT), 5 had 2 courses. Before HDCT all treated patients achieved a partial remission (15 patients after 3 courses VAD, 3 patients after 3 courses of VAD and 2 courses of velcade-doxorubicinprednisolone). The median time to disease progression was 33.1 (range 26-40) months; that of overall survival was 55.4 (range 2940) months.