Background. Anemia is the main symptom of multiple myeloma (MM) both at the time of disease onset and during tumor progression. Previously, the main method of anemia treatment was blood transfusion therapy. Currently, blood transfusions are supplemented by erythropoietin (EPO) administration. Safety and effectiveness of the drug have been proven in multiple trials including trials involving oncohematological patients.Aim. To present the results of using epoetin alpha (Eralfon) in patients with MM complicated by dialysis-dependent myeloma cast nephropathy in real clinical practice; to analyze the literature data on the use of EPO for the treatment of anemia in MM patients.Materials and methods. A retrospective analysis of a series of clinical observations was carried out: 4 patients with newly diagnosed MM at the ages between 52 and 60 years who underwent treatment at the Department of Hematology and Chemotherapy of Paraproteinemic Hemablastoses with a Bone Marrow and Hematopoietic Stem Cell Transplantation Block. All patients were diagnosed with myeloma cast nephropathy with significantly decreased glomerular filtration rate of 7–15 mL/min requiring renal replacement therapy. At the time of disease diagnosis, median hemoglobin level was 75 g/L, median creatinine level was 517.5 µmole/L. Endogenous EPO level was measured in all patients prior to epoetin alpha prescription: it varied between 2.31 and 149.6 IU/mL. Epoetin alpha (Eralfon) was prescribed at dose 12 000 IU – 0.3 mL subcutaneously 3 times a week. A review of the literature data on the use of EPO in patients with MM was conducted.Results. All patients at MM onset were dependent on renal replacement therapy and blood transfusion, therefore epoetin alpha was prescribed immediately. In case of renal function recovery and end of dialysis at target hemoglobin levels, administration of the drug was ceased. If dependence on renal replacement therapy persisted, epoetin alpha treatment continued as synthetic function of EPO-producing cells was compromised. In all clinical cases, epoetin alpha therapy was effective.Conclusion. Clot formation prevention should be kept in mind during epoetin alpha therapy. Decreased requirement for blood transfusions, improved quality of life with favorable safety profile of the drug make epoetin alpha an indispensable part of accompanying therapy in patients with MM and anemia.

Background. Autologous hematopoietic stem cell transplantation remains in demand for patients with hematological malignancies. The pool of hematopoietic stem cells is known to be heterogeneous. e studied various factors associated with previous treatment, patient and disease characteristics, as well as the composition of the C34+ pool in peripheral blood (), associated with the number of C34+ cells in the first leukocyte concentrate (LC).Aim. To determine the factors associated with C34+ , C34+ C143+ , C34+ C38– HLA-DR+/– and C34+ C38+/– HLA-DR– cells count in the first LC of patients with hematological malignancies.Materials and methods. Subpopulations of hematopoietic stem cells in the and first LC were studied in 80 patients with hematological malignancies (male to female ratio 1:1, median age 51 years). The control group included 24 healthy donors. Flow cytometry was used to determine the number of C34+, C34+ C38– HLA-DR+/–, C34+ C38+/– HLA-DR– and C34+ C143+ cells. Immunophenotyping was performed on samples of patients before mobilization and on the 1st day of leukapheresis, as well as on first LC samples on the 1st day of hematopoietic stem cells collection.Results. It was shown that the presence of early progenitor cells with C34+ C38– HLA-DR+/– immunophenotype in the before mobilization is associated with a higher first LC C34+ cells number (p = 0.003). In the presence of C34+ C38– HLA-DR+/– cells in the before mobilization, the median number of C34+ cells in the first LC was 2.6 %, and in their absence – 0.71 %. hen using granulocyte colonystimulating factor as monotherapy, the C34+ C143+ cells number in the first LC was significantly lower than when using chemotherapy and granulocyte colonystimulating factor (p = 0.03). However, the majority (9 of 16) of patients in the granulocyte colonystimulating factor monotherapy group had renal failure before mobilization. No factors associated with the number of C34+ C38– HLA-DR+/– cells in the first LC were found. In patients >60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old (p = 0.043). In patients with infectious complications during hematopoietic stem cell mobilization, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients without them (p = 0.019).Conclusion. The first LC number of C34+ cells is associated with number of C34+ C38– HLA-DR+/– cells, i. e. cells of the early differentiation stage with a high proliferation potential. A relationship was established between C34+ C143+ cells number before mobilization and first LC C34+ cells count: in the paired model – within the borderline values (p = 0.05), and in the multifactorial covariance model – with high significance (p = 0.0033). It has been proven that with increasing patient age and in the presence of infectious complications, the number of longterm repopulating C34+ C38+/– HLA-DR– cells decreases.

Background. One of the most common symptoms of multiple myeloma (MM) is pain. Bone pain is observed in 60– 80 % of patients at the disease onset. Neuropathic pain syndrome is also often found in MM.Aim. To characterize the pain syndrome in MM at the disease onset and various therapy stages.Materials and methods. From January 2019 to October 2021 a retrospective single-center study included 105 patients with newly diagnosed symptomatic MM (49 men, 56 women) aged from 26 to 83 years (median 58.5). Induction therapy in all patients was performed with bortezomib-containing regimens. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was performed in 44 patients. The Fisher–Freeman test was used to analyze contingency tables.Results. Pain syndrome of varying severity at the onset of MM was observed in 83 % of patients. The median time from the onset of pain to the diagnosis of MM was 120 days. In 62.5 % of patients with kidney damage and pain, analgesics (mainly nonsteroidal anti-inflammatory drugs) were used before the diagnosis of MM. In patients with pain syndrome, compared with patients without it, at the onset of MM, pathological fractures (p = 0.01), bone plasmacytomas (p = 0.0001), hypercalcemia (p = 0.03) were significantly more often detected, and stage III was diagnosed according to Durie– Salmon (p = 0.021). The incidence of peripheral toxic polyneuropathy was 35 %. Complete regression of polyneuropathy symptoms was observed in 19 % of patients, and a significant decrease – in another 62 % of cases. The main manifestation of pain syndrome during auto-HSCT was pain in the oral cavity due to mucositis of varying severity.Conclusion. Our study showed that MM patients mainly with stage III (86 % of cases) are referred for hospitalization to the National Medical Research Center for Hematology. Moreover, in 83 % of them the disease is accompanied by severe pain. More than a third of patients (35 %) developed bortezomib-induced peripheral polyneuropathy. Opioid analgesics are used for pain relief in the hospital, the indications for which were recorded in 45 % and 41 % of patients with MM during induction therapy and auto-HSCT, respectively.

Background. Data from real-life clinical practice studies provide additional information on the efficacy of new antitumor therapy regimens, including in patients who meet exclusion criteria for clinical trials.Aim. To evaluate the Isaomex triplet efficacy in multiple myeloma patients in real clinical practice.Materials and methods. From 2021 to 2024, the retrospective study included 83 double refractory multiple myeloma patients from 26 centers aged 38 to 85 years (median 63), who received the Isaomex triplet. Glomerular filtration rate ˂ 60 mL/min was detected at the time of isatuximabbased triplet initiation in 18 % patients, 2 of whom were on program hemodialysis. The median of previous therapy lines was 2 (1–6). The median time from diagnosis to initiation of isatuximabbased triplet therapy was 47 months (5–203). Survival curves were constructed using the Kaplan–Meier method. Statistical analysis was performed using Statistica 10 program.Results. Isaomex triplet therapy resulted in overall and renal responses in 76 % and 61 % of cases, respectively. The median progression free survival was 13.5 months. In the group of patients who did not receive daratumumab at previous stages, the median progression free survival was significantly higher and was 28 months vs 8 months (p ˂ 0.05). Threeyear overall survival was 81 %. Discontinuation of isatuximab due to the development of adverse event was recorded in 2 cases (2 %). In the group of patients with bone plasmacytomas (n = 46), Isaomex therapy resulted in an overall response rate of 67 %; 12‑month progression free survival was 48 %, and 1‑year overall survival was 76 %.Conclusion. The results of the Isaomex triplet use in real clinical practice for the treatment of relapsed multiple myeloma showed data comparable to the ICARIA registration study on the frequency of achieving a response, duration of progression free survival and overall survival. The triplet efficiency was shown in comorbid patients, with advanced stages and those undergoing renal replacement therapy.

The article presents the experience of the medical accreditation and simulation center of the "National Medical Research Center for Hematology" from March 2021 to January 2024.

Bone plasmacytoma is a malignant neoplasm consisting of plasma cells. It develops in the medullary cavities of the skeletal bones. The tumor can destroy bone cortex and proliferate into the surrounding tissues. In contrast to bone plasmacytomas, extramedullary plasmacytomas occur as a result of hematogenous dissemination in various tissues and organs. Based on literature data, the incidence of bone plasmacytomas at multiple myeloma (MM) onset is 7.0 % to 32.5 %, and at relapsed/progression ММ stages it is 9.0 % to 27.4 %. During bone plasmacytoma development, tumor cells acquire a number of new features: expression of adhesion molecules is decreased, new cytogenetic aberrations occur, autocrine secretion and neoangiogenesis are increased. The clinical course of MM complicated by bone plasmacytomas is characterized by minimal bone marrow damage, hemoglobin concentration within reference range, and decreased values of β2-microglobulin, paraprotein, calcium, and lactate dehydrogenase. Acute renal failure and immunoparesis are rare, early MM stages predominate. In literature, the MM form with multiple bone plasmacytomas is referred to as ‘macrofocal MM’. Survival rates of MM patients with bone plasmacytomas are at the intermediate level in terms of prognosis. The MM patients without plasmacytomas have the most favorable prognosis, whereas the MM patients with extramedullary plasmacytomas have the poorest prognosis. There is no unified approach to the treatment of MM complicated by bone plasmacytomas. There are no randomized prospective clinical studies on the efficacy of treating it. A successful use of proteasome inhibitors and immunomodulatory drugs was reported based on a small number of MM cases with plasmacytomas. Some studies proved the efficacy of auto-HSCT in this MM form. Bone plasmacytomas are treated with radiotherapy mainly after systemic chemotherapy.

Background. The problem of hemostasis system pathology in patients with AL amyloidosis (AL-A) is of great practical importance. Currently, there are no recommendations concerning indications and methods of prevention of thrombotic complications.Aim. To study the main parameters of blood coagulation system in patients with AL amyloidosis, to determine the indications for anticoagulant therapy, to evaluate the efficacy and safety of apixaban prophylactic use during antitumor therapy.Materials and methods. A prospective single-center study included 65 patients with newly diagnosed systemic AL amyloidosis. The median age was 58 (34–74) years. Induction therapy according to the program BorCyDex (bortezomib, cyclophosphamide, dexamethasone) was given to 59 (90 %) patients, of which 5 patients received the combination of BorCyDex with a monoclonal antibody to CD38 – daratumumab. The remaining 6 (10 %) patients were treated with melphalan. Patients with laboratory signs of hypercoagulability or thrombotic complications were treated with apixaban in therapeutic or prophylactic dose. Indications for apixaban therapy in therapeutic dose (10 mg/day): atrial fibrillation, arterial thrombosis or pulmonary embolism less than 1 year ago. Indications for apixaban therapy in prophylactic dose (5 mg/day) were considered the presence of one or more factors: hypoalbuminemia less than 20 g/L; increase in D-dimer level more than 500 ng/mL without instrumentally verified arterial or venous thrombosis; increase in D-dimer level more than 500 ng/mL within 3 months after resolved episode of thrombosis; increase in fibrinogen level more than 4 g/L; increase in FVIII activity more than 150 %. When two or more factors were present, an antiplatelet agent (acetylsacylicylic acid) was added to apixaban therapy. The follow-up period was 4–9 months (median 6 months).Results. Before the start of antitumor therapy, thrombotic complications were diagnosed in 15 (23 %), bleeding – in 3 (5 %) patients. Hemostasis study revealed an increase in one or more laboratory parameters reflecting hypercoagulability in 92 % of patients. Increase in fibrinogen level was found in 70 %, D-dimer – in 72 %, FVIII activity – in 92 % of patients. 3 (5 %) patients received a therapeutic dose of apixaban, 58 (89 %) patients ‒ a prophylactic dose. Therapy with apixaban and antiplatelet agent was performed in 10 (15 %) patients. During the follow-up 3 patients developed complications related to hemostasis system disorders: 1 (2 %) patient had thrombosis (ischemic stroke), 2 (3 %) – gastrointestinal bleeding of mild severity. All these patients received a prophylactic dose of apixaban due to the presence of 1 thrombosis risk factor: an increase in FVIII activity of more than 150 %.Conclusion. Clinical signs of hemostasis system pathology were observed in 28 % of AL amyloidosis patients, and laboratory signs of hypercoagulability were detected in 92 %. Our developed indications for thrombosis prophylaxis in AL amyloidosis were effective. The issue of FVIII activity increase as the only indication for anticoagulant therapy in AL amyloidosis patients requires further research.

Supportive therapy is becoming increasingly important for the state-of-the-art algorithm of multiple myeloma (MM) treatment. The introduction of innovative drugs and transplantation methods into clinical practice considerably improved the disease-free and overall survival rates. However, in the vast majority of cases, MM still remains an incurable malignant plasma cell tumor. It is often treated on a continuous basis with a succession of targeted drugs and integration of glucocorticosteroids and conventional cytostatic agents into the program therapy. All of these together with immunodeficiency, bone lesions, and myeloma nephropathy lead to a high risk of adverse events and cumulative toxicity of treatment. At the same time, one of the main goals at all MM therapy stages is to maintain quality of life. The characteristics of clinical symptoms, the nuances of targeted therapy and chemotherapy-associated adverse events justify the need for further development of supportive MM therapy algorithms which remain to be a matter of current concern. They should be mainly aimed at preventing the therapy complications, reducing the rate of adverse events and clinical manifestations of side effects as well as developing a treatment strategy for cumulative toxicity. In the state-of-the-art algorithm of program MM treatment, supportive therapy-related knowledge is of no less value than the information on antitumor drugs and their efficacy. This paper reports the personal experience and provides recommendations mostly based on the results of clinical studies or views of expert panels. It also offers practical recommendations for supportive therapy in symptomatic MM which include prevention of skeletal complications, thromboses, and infections, nausea and vomiting management, vaccination, pre-medication and the algorithm of monoclonal antibody administration, anesthesia, peripheral polyneuropathy treatment, correction of secondary immunodeficiency, nutritional support, fatigue assessment and countermeasures.

Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А). Materials & Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients. Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal. Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.

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.

Background. Medical care through telemedicine technologies for plasma cell tumors has been provided at the National Medical Research Center for Hematology since 2018. Patients are consulted at the “doctor–doctor” level in the field of “hematology”. Another important aspect of the application of telemedicine at the National Medical Research Center for Hematology is scientific, practical and educational activities aimed at developing remote interaction with medical institutions, developing ways to improve interaction with specialized medical organizations.Aim. To present the implementation of the main applications of telemedicine technologies on the example of paraproteinemic hemoblastoses.Materials and methods. From October 2018 to October 2022 the department of hematology and chemotherapy of paraproteinemic hemoblastoses with bone marrow and hematopoietic stem cells transplantation unit of National Medical Research Center for Hematology received 815 telemedicine requests (701 – primary, 114 – repeated). In 93.6 % of cases, telemedicine consultation was required for multiple myeloma, 2.6 % of requests included information about patients with solitary plasmacytoma, in individual cases, regional hematologists made inquiries about patients with plasma cell leukemia, plasmablastic lymphoma, Waldenstrom’s macroglobulinemia.Results. There has been an annual increase in the number of telemedicine consultations for multiple myeloma. Of the 73 participating regions, the most active were: Tambov Region, Altai Territory, Vladimir Region, Republic of Crimea, Republic of Buryatia, Krasnodar Territory, and Krasnoyarsk Territory. Most of the consultations are aimed at clarifying the tactics of treating multiple myeloma. In 20 % and 22 % of cases, first- and second-line therapy was recommended. In response to 21 % of requests, recommendations were given for the treatment of multiple myeloma complicated by double and triple refractoriness. In 14 % of requests, insufficient information content of medical documentation did not allow expressing an adequate opinion on the tactics of patient management. Hospitalization at the National Medical Research Center for Hematology for the purpose of autologous hematopoietic stem cells transplantation was recommended in 10 % of cases. An analysis of 4 % of telemedicine requests testified to the expediency of palliative treatment and local radiation therapy at the place of residence. The main disadvantages of requests are the lack of primary information when establishing a diagnosis and information on disease monitoring during therapy, as well as the presence of excessive information in medical records.Conclusion. An analysis of telemedicine consultations for paraproteinemic hemoblastoses over a 4‑year period indicates a high need for regional hematologists to discuss therapy tactics with doctors from the federal center. Through telecommunications between doctors of National Medical Research Center for Hematology and the region, in some cases, the full range of diagnostic and therapeutic measures is ensured, which contributes to improving the quality of medical care.

Imaging of bone lesions has an important role in diagnosis of multiple myeloma (MM) and evaluating the response to treatment. Computed tomography scan (CT) allows to detect osteolysis, plasmacytoma and the risk of fractures with high sensitivity. In the National Research Center For Hematologysince 2014 all patients with MM are diagnosed with the whole-body low-dose CT.The aim of the study was to demonstrate the sensitivity of the whole-body low-dose CT and to characterize localization, number and size of bone lesions in primary MM patients.Materials and methods. 50 patients with newly diagnosed MM were enrolled in the study. The diagnosis was established in accordance with international diagnostic criteria. All patients received the whole-body low-dose CT. According to the Durie-Salmon and ISS staging systems 62% and 66% of patients had stage III, respectively.Results. 96% of MM patients had bone lesions. In 30% of patients, bone involvement was the only criterion for CRAB. Pelvic bone lesions was most often diagnosed (92%). The destruction of the long bones of the arms and legs were most rarely detected (42% of patients) and mostly small. The presence of intraosseous plasmocytoma was noted in 40% of cases.Conclusion. The whole-body low dose CT was found to be the most sensitive modality for detection osteolytic bone lesions. Low-dose CT is available in MM case with bone disease only, for establish symptomatic stage. This patients require immedate antimyeloma treatment.

Aim. To study the efficacy and adverse event spectrum of high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal impairment, including hemodialysis (HD) dependence. Materials & Methods. The retrospective single-center study enrolled 64 MM patients (30 men and 34 women) with renal impairment, aged 19-65 years (median 54 years), who received auto-HSCT in the period from 2013 to 2019. Newly diagnosed patients had a median creatinine of 462 nmol/L and a median glomerular filtration rate of 10 ml/min/1,73 m2 (CKD-EPI). HD dependence was reported in 23 (36 %) patients on diagnosis date. As a result of the induction therapy, in 13 (57 %) out of 23 patients HD could be discontinued. Prior to auto-HSCT, overall antitumor response was 91 % (complete remission was 45 %), overall renal response was 80 % (complete renal response was 28 %). In the course of auto-HSCT 10 patients remained HD dependent. Two groups were analyzed: “HD-” (program HD-independent patients during auto-HSCT, n = 54) and “HD+” (program HD-dependent recipients of auto-HSCT, n = 10). Results. Herpes virus infection reactivation and reversible toxic encephalopathy were observed significantly more often in “HD+” than in “HD-” group (30 % vs. 6 %, p = 0.04 and 20 % vs. 0 %, p = 0.02, respectively). HD-dependent patients required red blood cell transfusion significantly more often than HD-independent patients (100 % vs. 35 % of cases; p = 0.0001). In 100 days after auto-HSCT, overall antitumor response increased from 91 % to 96 %, the rate of complete remission increased from 45 % to 64 %. After auto-HSCT the rate of complete renal response increased from 28 % to 34 %, however, overall renal response remained within the range of 80 %. After auto-HSCT, in a single case HD was discontinued. As a result of the treatment, 14 (61 %) patients became HD-independent. Transplantation-associated mortality was not reported. During median follow-up of 48 months, 5-year overall survival was 70 % and 5-year disease-free survival was 42 %. Conclusion. Auto-HSCT is a feasible, safe, and effective treatment of MM patients with acute renal impairment. Induction therapy with subsequent auto-HSCT resulted in less need for HD which was 36 % at MM onset and 14 % on completing the treatment.

Background. Plasmablastic lymphoma (PBL) is a rare variant of large B-cell lymphoma. This disease is usually associated with HIV infection and is predominantly identified in male patients. Tumor lesion is typically localized in oral cavity. PBL is characterized by aggressivity and low rate of long-term survival. Aim. To report a clinical case of a rare localization of PBL with primary impairment of bone marrow in a 19-year-old HIV-negative patient. Materials & Methods. The diagnosis of the disease turned out to be challenging and was based on the results of a multi-step complex immunohistochemical analysis of a bone marrow core biopsy sample. Results. Intensive block-based mNHL-BFM-90 polychemotherapy combined with bortezomib and daratumumab resulted in remission which allowed to perform consecutive autologous and then allogeneic hematopoietic stem cell transplantations. For the lack of immune control of transplant over the tumor the conducted therapy was disappointingly unsuccessful. The patient died in 11 months after diagnosis because of tumor progression. Conclusion. New approaches are definitely called for in order to explore methods of treating this complex disease. A study of mechanisms underlying PBL pathogenesis can contribute to better understanding of tumor biology and personalized choice of chemotherapy.

Background. Nowadays, hematology is a dynamically developing science due to the in-depth study of the molecular mechanisms of a particular disease. A better understanding of oncohematological diseases biology makes it possible to synthesize new targeted drugs, which have a favorable therapeutic effect. In particular, in multiple myeloma, after the introduction of proteasome inhibitors and immunomodulatory drugs into clinical practice, an improvement in overall survival was observed. However, characteristics of the mechanisms of transformation normal plasma cells into malignant ones are still difficult; therefore, the study of the pathobiological basis of multiple myeloma is currently an urgent task.The objective: to evaluate the possible influence of MAGE-C1 gene expression and the presence of mage-c1 protein in patients with newly diagnosed multiple myeloma on the anti-tumor response after bortezomib-containing therapy.Materials and methods. A prospective study included 33 multiple myeloma patients. The diagnosis was established according to International Myeloma Working Group criteria (IMWG, 2014). In 32 patients the induction therapy included bortezomib-containing courses, in one patient lenalidomide was included in the first-line regimens. The MAGE-C1 gene expression by real-time polymerase chain reaction and mage-c1 protein by immunohistochemistry in plasma cells bone marrow, were determined for all patients at the debut of multiple myeloma. As a control group was examined the bone marrow material of healthy donors.Results. When assessment the statistical relationship between the expression of MAGE-C1 gene and mage-c1 protein, it was found that there was no high expression of mage-c1 protein at low values of MAGE-C1 gene expression. At the same time, high expression of the gene was always associated with protein expression above normal values. The analysis aimed at finding the relationship between MAGE-C1 gene and mage-c1 protein detection and the degree of antitumor response after 6 courses of induction therapy showed that high expression of the studied parameters was associated with a worse response to bortezomib-containing treatment.Conclusion. We confirmed that the results of the two methods were comparable. Single factor analysis showed that patients with decreased MAGE-C1 gene and mage-c1 protein expression levels achieved a significantly higher antitumor response to bortezomib-containing regimens, while high expression was accompanied by refractoriness to bortezomib.

Background: Background: Multiple myeloma (MM) course is often complicated by extramedullary lesions - plasmacytomas, which pathogenesis is still not completely understood. Genome instability underlies dissemination in various neoplasias, including MM. An important manifestation of genetic instability is the loss of heterozygosity, i.e., the loss of the second allele in the regions of the genome featuring inherited polymorphisms. STR profiling is a method that allows simultaneously assessing the degree of DNA degradation and giving an integral assessment of the stability of the tumor genome. To assess the heterogeneity of MM, not only the tumor substrate in the bone marrow and plasmacytoma but also in circulating cell-free DNA (cfDNA) present in the peripheral blood plasma could be effectively analyzed. Methods: Methods: 11 of bone 6 plasmacytoma GeneMapper v.4 software (Applied Biosystems,

Proteasome inhibitors and immunomodulators (IMiDs), primarily bortezomib and lenalidomide, are essential components of treatment for both newly diagnosed and relapsed/refractory multiple myeloma (MM), producing high response rates and resulting in improved overall survival. However, bortezomib often induces a dose-limiting toxicity in the form of peripheral neuropathy (PN). Neurotoxicity often affects patient’s quality of life and requires dose modification or withdrawal of therapy, with a possible effect on the overall response. A prompt recognition of predisposing factors (such as diabetes mellitus, vitamin B12 deficiencies, or viral infections) and appearance of signs and symptoms, through a periodic neurological assessment with appropriate scales, is extremely important. Usually, bortezomib-induced PN is a sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution while motor neuropathy is less frequently observed. Dose adjustment of bortezomib could be necessary during treatment. Anticonvulsants (pregabalin, gabapentin, carbamazepine, etc.) and tricyclic antidepressants (amitriptyline) are most often used to relieve neurological pain. In this review we focus on the clinical manifestations of bortezomibinduced PN, current understanding of the pathophysiological mechanisms as well as clinical and pharmacological aspects of prevention and management this complication. New proteasome inhibitors such as ixazomib and carfilzomib do not have the neurotoxicity of bortezomib. An early switch within the class of proteasome inhibitors from bortezomib to oral ixazomib appears to be an important approach to prevent severe PN. Our own clinical case of an early switch from bortezomib-based induction to IRd triplet (ixazomib, lenalidomide, dexamethasone) is cited as an illustration of the success of this approach.

Background. Multiple myeloma (MM) is a hematological malignancy with plasma cells as substrate. Sometimes MM is characterized by plasmacytomas, i.e., intra- and extraosse-ous tumors. A paraffin block containing plasmacytoma substrate provides valuable material to be used for analyzing the molecular biological characteristics of tumor. STR-profil-ing is a method for simultaneous evaluation of DNA degradation and integral assessment of tumor genome stability. Aim. To describe STR-profiles of plasmacytoma DNA isolated from archival samples and to assess the integral stability of tumor genome against control DNA of patients. Materials & Methods. The retrospective study enrolled 10 MM patients with plasmacytoma (7 women and 3 men) aged 34-62 years (median 53.5 years) who were treated at the National Research Center for Hematology from 2013 to 2021. Paired tumor/control DNA samples were obtained from all 10 patients. Results. The present paper takes the first step in attempting a large-scale molecular genetic study of MM and provides first findings on the loss of heterozygosity (LOH) in plasmacytoma genome. All 10 patients showed LOH variants with different allelic loads having either deletion/ quantitatively neutral LOH or duplication of one of the two alleles and involving 1-8 STR-loci. In plasmacytoma substrate the number of loci with LOH tended to be higher in the group with MM relapses compared with plasmacytomas identified at disease onset. According to the data analysis, LOH was frequently (in 4 out of 10 cases) detected on chromosomes 1 (1q42), 6 (6q14), 7 (7q21.11), 13 (13q31.1), and 21 (21q21.1). Conclusion. The present paper shows the effectiveness of molecular analysis of DNAs being isolated from complex archival material consisting of paraffin blocks with plasmacytomas.

Background: Malignant plasma cells (PC) immunophenotype is well understood and represented by a large group of antigens expressed with varying frequency. Clusters of differentiation are both diagnostic and prognostic factors. Some of these serve as targets for monoclonal antibody and genetically engineered T-cells with chimeric antigen receptors in multiple myeloma (MM) patients. These molecules are SLAMF7 (Signaling lymphocytic activation molecule factor - CD319) and BCMA (B-cell maturation antigen - CD269). Membrane subunits of these molecules can be cleaved by enzymes (f.ex. γ-secretase) and released to the plasma as soluble proteins and can be easily detected using readily available commercial enzyme-linked immunosorbent assays (ELISA). SLAM family of receptors is a self-regulating and stimulates tumor proliferation. Therefore, soluble BCMA detection is one of the predictors of refractory disease. Aims: To compare the CD269, CD319 expression on malignant PCs and sBCMA, sSLAMF7 protein concentrations in serum of newly diagnosed multiple myeloma patients. Methods: The prospective study included 18 patients (8 women, 10 men) aged 26 to 70 years (median 54) with NDMM between June and September 2021. They received VRD induction therapy (2-4 cycles, median 4). Malignant PCs immunophenotyping was determined by multicolor flow cytometry (MFC) (CD319; CD269; CD138; CD38; CD19; CD45; CD81; CD27; CD20; CD56; CD200; CD117). Concentration of soluble BCMA, SLAMF7 in serum was detected using commercial ELISA (RayBio® Human CRACC/SLAM7 ELISA Kit, RayBio® Human TNFRSF17 ELISA Kit). Statistical analyses were performed using SPSS. Results: The results of the CD269, CD319 and sSLAMF7, sBCMA protein concentrations in the serum of NDMM patients are presents in Table 1. According to MFC of bone marrow malignant PCs, the presence of CD319 is detected in 90% of patients (n=16). sSLAMF7 protein is detected in the serum of 39% of patients (n=7) in the range of 1.14 to 5.43 ng/ml (median 2.9), in 61% of cases (n=11) sSLAMF7 wasn’t detected. In 56% of cases sSLAMF7 wasn’t detected, but CD319 was detected on the surface of malignant PCs. No cases of sSLAMF7 without the presence of CD319 on the malignant PC were detected in this study. CD269 was detected on malignant PCs in 45% of patients (n=8) and in 55% of cases (n=10) malignant PCs was CD269 negative. sBCMA was detected in 100% of patients (n=18). The concentration ranged from 122.33 to 11617.32 pg/ml (median 2139.7). In the group of CD269 positive patients, sBCMA concentration was significantly (p=0.001) higher than in CD269 negative group: medians were 5334.12pg/ml (1933.6-11617.3) vs 318.87pg/ml (122.3-3962.2), respectively. After induction therapy response was complete response in 16.5% (n=3), very good partial response in 12% (n=2), partial response in 66% (n=12), and progression disease in 5.5% (n=1). However, statistically significant correlations were not found between the depth of response, the presence of CD319, CD269 on the malignant PCs or/and the concentration of sSLAMF7, and sBCMA. Image:Summary/Conclusion: The high frequency of CD319-positive patients was not accompanied by detection of sSLAMF7 in 61% of patients. Whereas, 100% sBCMA detection in NDMM patients was not followed by CD269 detection on malignant PC in half of the patients. These findings may indicate both the heterogeneity of MM and the necessity for further studies of sBCMA and sSLAMF7 to determine their prognostic significance.