Multiple myeloma (MM) is a B cell lymphoproliferative disease characterized by clonal proliferation of plasma cells and heterogenous progression. Successes in MM therapy are in large part based on the study of molecular and genetic features of disease pathogenesis and identification of high-risk chromosomal abnormalities determining prognosis and antitumor response. Elderly patients with newly diagnosed MM with high-risk cytogenetics who are not candidates for autologous stem cell transplantation should receive programs of antitumor therapy which increase progression-free survival and overall survival with satisfactory tolerability and minimal toxicity. Use of monoclonal antibodies in triplets at early stages allow to achieve deeper antitumor response, the absence of minimal residual disease in a greater number of observations, and improve survival in all patient subgroups.A clinical observation of a 75-year-old female patient with newly diagnosed MM with high-risk cytogenetics and multiple bone plasmacytomas with massive extraosseous components is presented. During D-Rd regimen therapy, after 8 daratumumab administrations very good partial remission was achieved which has been maintained for 20 months. Significant improvement in quality of life with satisfactory treatment tolerability and absence of adverse events are observed

Study of the molecular pathogenesis of multiple myeloma led to development and introduction of antitumor agents with new mechanisms of action and their combinations into clinical practice. According to several trials, use of anti-CD38 monoclonal antibody daratumumab as part of triplet therapies at an early stage leads to deep and long-term antitumor response, achievement of MRD-negative status, and, as a result, increased survival and improved prognosis in all patient subgroups. High effectiveness of daratumumab subcutaneous formulation close to intravenous formulation has favorable safety profile, short administration time and low rate of infusion reactions which improves patients’ quality of life, affects their treatment compliance, and decreases healthcare costs. We present a clinical observation of a 60-year-old patient with newly diagnosed multiple myeloma who previously underwent treatment for another lymphoproliferative disorder which included autologous hematopoietic stem cell transplantation leading to complete and long-term remission. After 9 intravenous daratumumab infusions (with recommended dose of 16 mg/kg) in accordance to the D-Rd regimen, evaluation of antitumor effect and consideration of socially active lifestyle of the patient, daratumumab formulation for intravenous administration was replaced with subcutaneous formulation of fixed dose 1800 mg. Further deepening of the antitumor response was observed along with manageable safety profile and absence of significant adverse events which allowed to maintain intercourse intervals and improve the patient’s quality of life.

Background. Melanoma of the skin is characterized by a rapid progression and early metastasis. It has been shown the disseminated tumor cells, which are often found in the bone marrow, has an important prognostic value. The study of disseminated tumor cells in melanoma might be one of the possible additional sources of information about the nature of the disease and potential application points for drug therapy. Aim. To study the frequency of detection of disseminated tumor cells in the bone marrow in melanoma, depending on the clinical and morphological characteristics of the tumor. Materials and methods. The study included 67 patients with a verified diagnosis of melanoma who were examined and treated at the Blokhin National Medical Research Center of Oncology from 2014 to 2019 years. Male patients accounted for 50.7% (n=34), female patients 49.3% (n=33). The average age of patients: 50.11.6 years. Immunological and morphological examination of the bone marrow were perfomed. Morphological examination was performed by two independent morphologists. Disseminated tumor cells were evaluated by flow cytometry among all nucleated cells (Syto41+) based on the expression of the HMB-45 antigen and the absence of expression of the CD45 panleukocyte antigen (FACS Canto II, USA, Kaluza Analysis v2.1). Statistical data processing was performed using the IBM-SPSS Statistics v.21 Results. Morphologically bone marrow damage was not detected in any case. Disseminated tumor cells (CD45-HMB-45+) in the bone marrow of melanoma patients were detected in 62.7% (n=42) of cases by flow cytometry. The frequency of bone marrow damage in the early stages is not lower than in advanced ones (p=0.029). This is clearly seen in the enlarged analysis. The percentage of DTC detection. At stages I and II was 60.0% (6/10) and 84.6% (11/13), respectively, at stages III and IV 44.4% (8/18) and 65.4% (17/26). In addition, the frequency of detection of disseminated tumor cells in the bone marrow was higher in young patients (p=0.02). There was no correlation between the frequency of bone marrow damage depending on BRAF status. Conclusion. The connection of disseminated tumor cells with the clinical and morphological characteristics of the melanoma has been established. Melanoma is characterized by frequent bone marrow damage, even in the early stages, in young patients.

Use of microinfusion elastomeric pumps for extended administration of antitumor drugs improves patients’ quality of life during prolonged cyclic treatment because of the absence of venous complications and infusion allergic reactions during administration of cytostatic agents and targeted drugs.

Multiple myeloma (MM) is a B-cell lymphoproliferative disorder. Its morphological substrate is plasma cells producing monoclonal immunoglobulin. Monoclonal light chains damage nephrons leading to development of acute kidney failure (AKF) which can be diagnosed at MM onset, recurrence, or progression. Dialysis-dependent kidney failure (DDKF) is associated with worse prognosis and decreased overall survival. Currently, the standard of MM therapy complicated by moderate and severe AKF is programs including bortezomib. According to the results of completed trials, achievement of hematological response plays the main role in AKF resolution, therefore, the use of new highly effective regimens of antitumor drug therapy is recommended. Despite the results of large clinical trials showing the effectiveness of daratumumab in therapy of patients with MM, data on its use in patients with newly diagnosed MM complicated by DDKF who are candidates for autologous hematopoietic stem cell transplant are limited. A case of daratumumab therapy (as monotherapy and in combination with lenalidomide, dexamethasone) of a 38-year-old female patient with MM complicated by DDKF and significant adverse events developed during previous short-term treatment with bortezomib is presented. The achieved hematological response (partial remission, absence of minimal residual disease), satisfactory somatic condition, as well as favorable daratumumab safety profile allowed to consider the patient for autologous hematopoietic stem cell transplant and increased the probability of improved renal response with subsequent cancellation of hemodialysis.

Despite the therapy advances, largely due to the study of molecular biology, multiple myeloma remains an incurable disease, and refractory course or relapses significantly worsen the prognosis. In this regard, the development of effective therapeutic agents with fundamentally new mechanisms of action that provide increased survival is currently an urgent task. One potential immunotherapeutic target is signaling lymphocyte activation molecules (SLAMs), and the anti-SLAMF7 monoclonal antibody elotuzumab is used in combination with either lenalidomide and dexamethasone (Elo-Rd regimen) after 1 prior line of therapy, or with pomalidomide and dexamethasone (Elo-Pd regimen) after 2 or more lines of therapy. The results of studies demonstrated a survival benefit in all subgroups of patients with refractory or relapsed multiple myeloma when using elotuzumab. A manageable safety profile and a low frequency of grade III–IV induced myelosuppression were noted, which allows the use of elotuzumab in combination with lenalidomide or pomalidomide and dexamethasone in elderly and debilitated patients. We present our own experience of using elotuzumab in the treatment of patients with refractory/recurrent multiple myeloma. A clinical case of a patient in whom treatment with elotuzumab was initiated at an early stage (after 1 line of previous therapy) is presented; the effectiveness and safety of using the monoclonal antibody are assessed. A significant improvement in the patient’s clinical condition and positive dynamics according to laboratory data were noted already during the 1st cycle of Elo-Rd regimen with a further progressive deepening of the antitumor response along with satisfactory tolerability and the absence of significant adverse events.

Multiple myeloma is a malignant tumor characterized by the proliferation of clonal plasma cells and currently remains an incurable disease, despite advances in therapy. Resistance and development of double refractoriness represent a significant problem, worsening the prognosis. To overcome double refractoriness, new proteasome inhibitors carfilzomib and ixazomib, the 3rd generation immunomodulator pomalidomide and monoclonal antibodies daratumumab, elotuzumab and isatuximab are used. Based on randomized phase III ICARIA-MM and IKEMA studies results, which demonstrated, along with a manageable safety profile, advantages in increasing the antitumor response depth, the rate of achieving negative minimal residual disease status and survival in all subgroups of patients with refractory/relapsed multiple myeloma, isatuximab is used in IsaPd (isatuximab, pomalidomide, dexamethasone) and IsaKd (isatuximab, carfilzomib, dexamethasone) combination. This article discusses the clinical pharmacology of isatuximab. The results of studies demonstrating the effectiveness and safety of antitumor therapy regimens including isatuximab, which made it possible to use it in clinical practice, are presented. We present a case report of a patient with refractory/relapsed multiple myeloma who received 3 lines of antitumor treatment, including class 2 proteasome inhibitors, lenalidomide and the monoclonal antibody elotuzumab. After 3 cycles of IsaPd (8 injections of isatuximab), partial remission and pain relief were recorded. The achieved antitumor effect, along with the absence of significant adverse events, facilitated the continuation of therapy at recommended doses.

Plasma cell leukemia (PCL) is a rare malignant plasma cell neoplasm with aggressive clinical progression, minimal response to therapy and unfavorable prognosis. Concomitant new coronavirus infection COVID-19 and its complications significantly worsen prognosis in patients with PCL. Currently, approaches to PCL therapy are not finalized, and regimens developed for multiple myeloma are used. In PCL, the most common clinical symptoms are renal failure and hypercalcinemia which are frequently observed in multiple myeloma. Therefore, use of proteasome inhibitor (bortezomib) with proven effectiveness in multiple myeloma, is justified. A clinical observation of a 64-year-old female patient who was hospitalized in poor physical condition with the new coronavirus infection COVID-19 is presented. During hospitalization, debut of PCL was suspected, and as soon as possible after diagnosis confirmation using vital indications, antitumor drug therapy was started with positive effect.

Multiple myeloma (MM) is a B-cell malignant tumor; its morphological substrate – plasma cells – produces monoclonal immunoglobulin. Primarily, MM is diagnosed in elderly people and is characterized by a variety of clinical manifestations caused by plasma cells infiltration and organ damage. Despite successes in MM therapy, in the majority of cases recurrences of MM or refractory process are observed. In this case, the choice of antitumor drug is usually made depending on its tolerability, toxicity, and availability. Selection of correct treatment can be complicated by such frequent clinical manifestations of MM as osteolytic vertebral lesions leading to development of pathologic compression fractures which in some cases cause spinal cord compression and full immobility in the patients with MM.A clinical case of a 62-year-old female patient with refractory MM is presented. Pathologic compression fractures of the Th12 and L2 vertebral bodies with massive extraosseous component at the Th12 vertebra level posed a threat of spinal cord compression. At the 1st stage, percutaneous vertebroplasty was performed, then antitumor therapy with daratumumab without increased intercycle intervals which significantly increased patient’s quality of life.

Between July 2005and October 2006, eight patients (pts) with hairy cell leukaemia were treated with Vero- cladribine at N.N. Blokhin Cancer Research Center. All pts achieved complete remission (CR). Duration of CR ranges from 1+ to 12+ months in 7 cases. There were no serious adverse events during the treatment and follow-up periods (1-12 months). Vero- cladribine was well tolerated. Anemia (grade IV) was seen in 1 patient and thrombocytopenia (grade I) was seen in another 1 patient. No one patient has febrile neutropenia or infectious complication.

Multiple myeloma is a B-cell lymphoproliferative disorder. Morphological substrate of the disorder are plasma cells producing monoclonal immunoglobulin, and the disorder is characterized by heterogeneity of clinical manifestations. Due to the understanding of molecular and biological basics of multiple myeloma pathogenesis, significant success was achieved in treatment of the standard and high-risk cytogenetics groups including full remission. However, not all patients show long-term progression-free survival. Necessity of more accurate evaluation of the extent of antitumor response, prognosis of progression-free survival and recurrence development led to minimal residual disease (MRD) testing. The analysis is based on detection of phenotypically aberrant clonal plasma cells in bone marrow aspirate after drug treatment. Currently, MRD-negative status is a significant prognostic factor. In some studies, high effectiveness of daratumumab in achievement of MRD-negative status in elderly patients with newly diagnosed multiple myeloma was demonstrated.

Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19-, CD56+, CD45- plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important. Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages. Materials & Methods. The present study enrolled 62 MM patients aged 31-76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards. Results. At the stage of primary diagnosis of MM, the imunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off > 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.

Background. Nowadays, one of the promising areas is the study of bone marrow in malignant tumors. It is known that hematogenous metastasis to the bone marrow in cancer is a common event. Identification of bone marrow lesions in ovarian cancer, as well as the study of hematopoiesis, can provide additional information about the features of metastasis of this tumor and will make it possible to assess the prospects for targeted therapy. Aim. To assess the possibility of detecting disseminated tumor cells in the bone marrow in patients with ovarian cancer, to establish the frequency of bone marrow damage and to analyze the relationship with the clinical and morphological parameters of the tumor. Materials and methods. This work includes 42 patients with ovarian cancer who received treatment at the Blokhin National Medical Research Center of Oncology. The study was carried out by morphological and immunological methods. Morphological examination of the bone marrow (counting myelograms, calculating myelogram indices, detection of tumor cells) was performed by two morphologists. Disseminated tumor cells were detected using flow cytometry (FACS Canto II, USA, Kaluza Analysis v2.1 software). Monoclonal antibodies were used: CD45, EPCAM. Results. Disseminated tumor cells in the bone marrow of patients with ovarian cancer were determined based on the expression of the EPCAM antigen and lack of expression of CD45 antigen. Disseminated tumor cells were found in 65.2% (n=15)of bone marrow aspirates. Disseminated tumor cells did not correlate with tumor size, lymph nodes status and stage. The frequency of bone marrow damage was higher at stage III and reached 78.6% (11 out of 14 patients), while it was 33.3% (1 of 3 patients) in stage I. 40.0% of positive cases (2 out of 5 patients) were detected at stage IV. Disseminated tumor cells were found in 78.6% (n=11) of bone marrow aspirates in primary ovarian cancer, while in recurrent ovarian cancer they were found only in 44.4% (n=4). Conclusion. The hematogenous dissemination of ovarian cancer in the bone marrow was established. Bone marrow lesions was noted even in the early stages of the tumor process. The frequency of detection of disseminated tumor cells in the bone marrow of patients with ovarian cancer was 65.2%. More frequent bone marrow damage was noted in primary ovarian cancer. The number of myelocytes was significantly lower in primary ovarian cancer without bone marrow damage. The number of lymphocyte was lower in cases of bone marrow lesions.

Myeloma is an oncological disease characterized by uncontrolled formation of plasma cells in the bone marrow leading to destruction of bone tissue and accompanied by anemia and kidney failure. Morbidity is 1–2 % among all malignant tumors. Specific antitumor therapy in conjunction with bone marrow transplant allows to achieve satisfactory long-term outcomes. It should be noted that during therapy various complications are quite common, as well as exacerbation of concomitant pathology which can transform into a competitive disease at any moment. A clinical observation of treatment of a patient with myeloma and diverticulosis of the colon complicated by acute diverticulitis with paracolic infiltrate formation is presented.

Introduction. An important aspect of cancer treatment today is the concept of immuno-targeted therapy, which requires a deep understanding of the characteristics of immune reactions in the body of a cancer patient. Bone marrow is the central organ of immunopoiesis, therefore, along with the study of tumor characteristics, attention is paid to the bone marrow. The study of the cellular composition of the bone marrow in some types of cancer revealed a number of features of hematopoiesis, which requires further deeper analysis.Purpose. To study the parameters of hematopoiesis in patients with primary and recurrent ovarian cancer.Materials and methods. The paper presents data from 68 patients with a verified diagnosis of primary (n = 43) and recurrent (n = 25) ovarian cancer. The study was dominated by serous adenocarcinoma of high grade. Stage I was established in 13.2 % of cases, II – in 5.9 %, III – in 60.3 %, IV – in 20.6 %. The bone marrow was harvested by puncture of the posterior iliac spine (spina iliaca posterior superior). Parameter assessment and myelogram calculation were performed by two physicians, morphologists. The content of myelokaryocytes, indicators of granulocyte, erythroid lineage, the content of lymphocytes, monocytes were analyzed, and myelogram indices were assessed. In all patients microscopy of bone marrow samples excluded metastatic lesions. Statistical data processing was performed using the SPSS Statistics v. 21 package.Results. The analysis of bone marrow samples from patients with ovarian cancer revealed differences with the norm for both primary and recurrent ovarian cancer. Most punctates were normocellular, but average myelokaryocyte count in both groups was below normal. With recurrent ovarian cancer, a reduced content of promyelocytes and metamyelocytes was noted, whereas with primary cancer, all young forms of neutrophils was below normal. An increase in segmented neutrophils without a change in the percentage of cells of the granulocytic lineage was observed in primary ovarian cancer, and in one third of the samples of bone marrow an increased number lymphocytes and monocytes were noted. With recurrent ovarian cancer lymphocytes were increased in 2/3 of samples, monocyte – in 48 %. A change in the proportion of cells of the erythroid lineage was observed in both recurrent and primary cancers: depletion of the pool of basophilic normoblasts and polychromatophils with an unchanged number of erythrokaryocytes, an increase in oxyphilic forms were noted.Conclusion. The revealed changes in hematopoiesis in ovarian cancer reflect the aggressive course of high-grade tumors, which can be considered as a result of the systemic influence of the tumor, and the obtained data can serve as the basis for a detailed immunophenotypic study of bone marrow in ovarian cancer.

Chronic myeloproliferative neoplasms (CMPN), Ph-negative, are of clonal nature, develop on the level of hematopoietic stem cell and are characterized by proliferation of one or more hematopoietic pathways. Currently, the group of Ph-negative CMPN includes essential thrombocythemia, primary myelofibrosis, polycythemia vera, myeloproliferative neoplasm unclassifiable.Identification of mutations in the Jak2 (V617F), CALR, and MPL genes extended understanding of biological features of Ph-negative CMPN and improved differential diagnosis of myeloid neoplasms. Nonetheless, clinical practice still encounters difficulties in clear separation between such disorders as primary myelofibrosis, early-stage and transformation of essential thrombocythemia into myelofibrosis with high thrombocytosis. Thrombocytosis is one of the main risk factors for thromboembolic complications, especially in elderly people.A clinical case of an elderly patient with fracture of the left femur developed in the context of Ph-negative CMPN (myelofibrosis) with high level of thrombocytosis is presented which in combination with enforced long-term immobilization and presence of additional risk created danger of thrombosis and hemorrhage during surgery and in the postoperative period.

Introduction. One of the serious complications after transplantation of solid organs and bone marrow is the development of post-transplant lymphoproliferative diseases.Clinical case. To evaluate the course of post-transplant lymphoproliferative diseases in the long-term in a liver transplant recipient after conversion of immunosuppressive therapy from tacrolimus to everolimus. We analyze a case of generalized primary plasmacytoma of lymph nodes with bone marrow involvement in a patient after liver transplantation.Results. After conversion of immunosuppression we observed a rapid positive trend: decreasing size of lymph nodes and regression of the level of paraprotein down to its complete disappearance. There were neither adverse events associated with everolimus for four years, nor signs of immunosuppression insufficiency.Conclusion. This Case Report is the first description of a long-term remission of nodal plasmacytoma that developed in a liver transplant recipient after complete withdrawal of calcineurin inhibitors and administration of everolimus. We suggest that the regression of post-transplant lymphoproliferative diseases after replacing calcineurin inhibitors with everolimus is associated not only with the minimization of calcineurin inhibitors exposure, but also with the antitumor effect of the everolimus itself, which prompts us to discuss the possibilities of expanding its clinical application.

Evaluation of minimal residual disease (MRD) on the 15th day of treatment of acute lymphoblastic leukemia from B-linear precursors (B-ALL) in children is of key importance in the prognosis of the disease. When evaluating the MRD, it is necessary to take into account the features of the primary immunophenotype of tumor B-lymphoblasts. To assess the MRD on the 15th day of treatment several immunological approaches have been proposed that have a general concept, but differ in fundamentally important details. The purpose of this work was to analyze the established flow cytometry (FC) protocols of the main research groups (BerlinFrankfurt-Munster Group, St. Jude Hospital, Children’s Oncology Group) and to compare the results evaluated according to those approaches. This study was approved by the Independent Ethical Committee N.N. Blokhin National Medical Cancer Research Center. The study included 131 patients with B-ALL aged 1 to 17 years (median 5.53). Pre-Pre-B immunosubvariant prevailed (92.4%). A morphological (myelogram count) and immunological (MRD assessment) study of the BM was performed in all patients on the 15th day. Comparing the FC protocols of the MRD on the 15th day, it was shown that CD10 was a more reliable criterion for the detection of B-LP in comparison with CD34. The expression of CD45 may serve as an additional criterion for the detection of B-LP. The recalculation of the mononuclear cells is a more stringent criterion for determining the MRD. The scientific novelty is that for the first time on the 15th day, a detailed comparison of flow cytometry data with a cytological picture of the bone marrow was carried out. It was shown for the first time that not all B-LP detected on the basis of CD10+ /CD19+ /CD34+ /CD45low are aberrant according to CD58/CD38.

Introduction.Detection of disseminated tumor cells (DTC) in solid tumors is an important component of the assessment of disease prognosis. Bone marrow damage is common. There is evidence indicating an important role for bone marrow lymphocyte subpopulations in hematogenous metastasis. Aim.To evaluate the frequency of bone marrow damage in patients with non-small cell lung cancer (NSCLC) based on the detection of DTC by flow cytometry, as well as their effect on the population of bone marrow lymphocytes. Materials and methods.62 bone marrow samples of patients with a verified diagnosis of NSCLC: adenocarcinoma (33), squamous cell carcinoma (27), other types (2). Methods: morphological, multicolor flow cytometry. Studied DTC, lymphocyte populations CD3, CD4, CD8, CD19, CD20, CD16, CD27. Collection and analysis: FACS Canto II, USA, Kaluza Analysis v2.1. Results.In bone marrow, DTC (EPCAM+CD45-) were found in 43.5% of patients with NSCLC (1 cell per 10 million myelocariоcytes was taken as the threshold value). The presence of DTC did not correlate with the size of the tumor, the status of the lymph nodes, and the stage of the tumor process. DTC was more often observed in more differentiated tumors (p=0.023). A significant increase in the level of subpopulations of CD16+CD4-NK-cells (p=0.002), CD27+CD3+T-cells (p=0.015) with bone marrow damage was revealed. Conclusion.The possibility of detecting DTC in the bone marrow of patients with NSCLC was established, in 43.5% of patients with NSCLC in the bone marrow DTC was detected, and their presence was established even with a localized tumor process. More frequent bone marrow damage was observed with well-differentiated tumors. The relationship between DTC and bone marrow lymphocyte populations was revealed: subpopulations of CD16+CD4-, CD27+CD3+.