Комплексное применение методов лучевой диагностики у пациентки с множественной миеломой (клиническое наблюдение)

The article presents the possibilities of the complex application of methods of radiation diagnostics: bone x-ray, dual-energy X-ray absorptiometry, computed tomography, positron emission tomography combined with computed tomography using fluorodeoxyglucose labeled with 18-fluorine (PET/CT with 18F-FDG) in a patient with multiple myeloma, which was treated in the amount of high-dose therapy with autologous transplantation of hematopoietic stem cells. The diagnosis was established immunohistochemically. The use of these methods allowed us to dynamically assess the pathological changes characteristic of multiple myeloma.В статье представлены возможности комплексного применения методов лучевой диагностики: рентгенографии костей, двухэнергетической рентгеновской абсорбциометрии (ДРА), компьютерной томографии (КТ), позитронно-эмиссионной томографии, совмещенной с компьютерной томографией c применением фтордезоксиглюкозы, меченной 18-фтором (ПЭТ/КТ с18F-ФДГ), у пациентки с множественной миеломой, которой проводилось лечение в объеме высокодозной химиотерапии (ВДТХ) с последующей аутотрансплантацией гемопоэтических стволовых клеток (аутоТГСК). Диагноз был установлен иммуногистохимически. Применение этих методов позволило в динамике оценить патологические изменения, характерные для множественной миеломы

Proteasome inhibitors: situation and prospects (literature review and own data)

Multiple myeloma is a clonal B-cell malignancy characterized by proliferation of plasma cells that accumulate mainly in bone marrow and usually secrete monoclonal Ig and/or Ig light chains. The history of therapy development in this disease has more than 50 years. After ubiquitin-proteasome system of apoptosis become apparent bortezomib has been included in the mains therapy regimes. Simultaneously, the group of proteasome-inhibitor drugs is continually developing and opening more therapeutic options in refractory or relapse forms

Anemia of chronic diseases: the important aspects of pathogenesis and treatment

The review contains data about new important aspects of pathogenesis, and treatment of anemia of chronic diseases. The treatment of patients with anemia of chronic diseases by erythropoiesis-stimulating agents and iron is analyzed

Chronic lymphoproliferative diseases: survival in cohort study of 310 patients (single-center study results and literature data)

Introduction. Chronic lymphoproliferative disease (CLPD) are common hematologic malignancies, accompanied by highly variable clinical course, different prognosis and understudied survival as one of the main criteria for long-term treatment efficacy, especially outside of clinical trials.Materials and methods. Patients with CLPD (n = 310) treated in hematology center of Burdenko Main Military Clinical Hospital from June 2003 to September 2014 are included in the study. The diagnosis of specific nosology verified in accordance with national and international recommendations. Analysis of study outcomes was based on overall survival (OS) using the Kaplan–Meier method.Results and discussion. Most patients (mainly with non-Hodgkin»s lymphoma (NHL) – 75 %, or multiple myeloma (MM) – 80.6 %) had advanced disease (III–IV), and 20.3 % admitted to the hospital in poor general condition (ECOG somatic status – 3–4). A significant proportion of patients (38.3 %) with NHL and Hodgkin lymphoma (HL) had a large tumor masses. Median of OS in patients with CLPD was 81.1 months. 5-year survival of total patients from time of diagnosis was 62 %, 10-year survival rate – 37 %. Patients with MM have shortest median of OS – 39 months, while patients with chronic lymphocytic leukemia (CLL) have the longest – 117.8 months. Median OS for NHL patients was 68.1 months, for HL patients – 99.3 months. When comparing survival for two time intervals (2003–2009 and 2009–2014), a tendency to increasethe survival rate for certain groups of patients with CLPD was revealed, that could be due to target therapy and new therapeutic approaches.Conclusion. New drug efficacy for certain diseases has led to renewed interest in the results of CLPD therapy. In our study, most CLPD patients have long-term OS, but the subsequent therapy lines influence on OS requires further study. These results will contribute to new developments in the organization and planning of therapy, changes in therapeutic practice and individualization of treatment.</p

The role of paraproteins in kidney damage in patients with lymphoproliferative diseases

Background. The course of lymphoproliferative diseases, in which the proliferation of a malignant clone is accompanied by the secretion of paraproteins, is often complicated by kidney damage. Perhaps kidney damage is associated with the physicochemical properties of monoclonal proteins.The objective of the study was to determine the relationship between the type of monoclonal paraprotein, its level of secretion, and kidney damage in lymphoproliferative diseasesMaterials and methods. A retrospective analysis of the data of 108 patients with lymphoproliferative diseases accompanied by paraproteinemia and kidney damage was performed. The age of the patients was 31–86 years (median 62.5 years). 78 out of 108 patients were diagnosed with chronic kidney disease (CKD). CKD was diagnosed in accordance with the clinical guidelines of KDIGO 2012.Results. In patients with multiple myeloma, stage III CKD was diagnosed in 28 (35.9 %) cases, stage IV – in 14 (17.9 %), stage V – in 19 (24.4 %). High risk group for CKD included 10 (9.3 %) of 30 patients without CKD. 91 patients were diagnosed with concomitant diseases predisposing to the development of kidney damage. In the group of patients with paraproteinemic hemoblastosis in combination with CKD, the vast majority were patients with the presence of IgGκ and IgGλ blood paraproteins, free light chains (FLC), and Bence-Jones protein (BJ) in the urine. At the same time, patients with the secretion of IgDλ, IgAλ, IgAκ and IgMκ paraproteins were much less common. The highest level of pathological Ig of all classes and their structural components and fragments was observed in patients with stage III CKD, which is also characteristic of other laboratory markers in CKD. A negative correlation of glomerular filtration rate (GFR) with FLCκ in the blood (r = –0.21), GFR with BJκ (r = –0.35), GFR with FLCλ in the blood (r = –0.13), GFR c BJλ, which indicates a tendency to damage the kidneys of FLC and protein BJ.Conclusion. In patients with lymphoproliferative diseases accompanied by monoclonal secretion of paraprotein and kidney damage with the development of CKD, in most cases IgGκ, IgGλ, FLCκ and FLCλ were determined in the blood, and protein BJ in urine. IgAκ, IgAλ, IgMκ, IgMλ, IgDλ paraproteins were determined much less frequently in serum. The highest level of pathological Ig and their structural components was observed in patients with stage III CKD. No association with quantitative level, type of paraprotein, and kidney damage was found. The role of FLC and BJ protein in the development of nephropathy is noted. The results of the study also show that with the development of the disease and kidney damage with subsequent progression of the stage of CKD in patients with lymphoproliferative diseases and proteinemia, there is a tendency to a temporary decrease in proteinuria and a compensatory increase in the number of paraproteins in the blood. This can be considered as one of the compensatory pathophysiological mechanisms of the protective function of the kidneys

Pathogenetic features of anemia of chronic diseases in patients with malignant neoplasms and rheumatic pathology

Objective: to study the importance of cytokines, hepcidin, a soluble transferrin receptor, iron metabolism in the development of anemia of chronic diseases in patients with malignant neoplasms and rheumatic pathology, to identify the leading factors in the development of anemia for each of the studied groups and to develop a working classification of anemia of chronic diseases.Materials and methods. 63 patients with rheumatic pathology were examined. The study group included 41 (17 men/24 women, average age 53.4 ± 4 years) patients with anemia, the control group included 22 (9 men/13 women, age 49.3 ± 1.78 years) patients without anemia. The patients (n = 63) with stage II–IV malignant neoplasms were examined. The study group included 41 patients with anemia (34 men/7 women, age 67.1 ± 9.9 years), in the control group 22 patients without it (17 men/5 women, age 60.2 ± 14.9 years). The number of red blood cells, the hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, concentrations of serum iron, total iron binding capacity (TIBC), ferritin, transferrin, C-reactive protein (CRP), transferrin saturation index (TSI), and soluble transferrin receptor (sTfR), hepcidin, interleukin (IL) – 6, – 10, tumor necrosis factor-α (TNF-α) were determined. Mann – Whitney U Test was applied to check for statistically significant differences in study samples.Results. Compared with the control group, elevated concentrations of ferritin, CRP, hepcidin, sTfR and IL-6 (p &lt;0.05) were found for patients with rheumatic pathology and anemia and no differences were found in the concentrations of iron, TIBC, TSI, transferrin. For patients with solid malignant neoplasms and anemia, lower concentrations of iron, TIBC, TSI and higher concentrations of CRP, hepcidin, sTfR, IL-6, IL-10, TNF-α (p &lt;0.05) are shown in comparison with the control group and there were no differences in the concentrations of ferritin, transferrin (p &gt;0.05).Conclusion. The multicomponent anemia genesis in patients with cancer and rheumatic pathology is shown. The contribution of each mechanism to the development of anemia may vary depending on the specific nosological form. In patients with cancer, functional iron deficiency, activation of IL-6, IL-10, TNF-α synthesis and an increase in hepcidin synthesis lead to the development of anemia of chronic diseases. In patients with a rheumatic profile and anemia, a more pronounced synthesis of hepcidin and an increase IL-6 concentration are indicated. A working version of the classification of anemia of chronic diseases based on the leading pathogenetic factor is proposed (with a predominant iron deficiency, with impaired regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin)

The late extramedullary relapse of the multiple myeloma with a predominant lesion of the duodenum and pancreas (clinical observation and mini-review)

A rare case of the multiple myeloma is written. The patient developed the extramedullary lesions with a primary lesion of the duodenum as a massive plasmacytoma with the bleeding, as well as damage to the pancreas and lymph nodes. The patient received several lines of therapy, including proteasome inhibitors and antitumor immunomodulators before the onset of extramedullary lesions. Extramedullary relapse was detected by positron emission tomography combined with CT (PET/CT) before the appearance of obvious clinical signs, which emphasizes the advisability of including PET/CT in the diagnostic algorithm for such patients. Repeated therapy with the previously used bortezomib or lenalidomide was ineffective, there was a further increase in plasmacytoma in duodenum and its bleeding, which led to severe anemia. The combination of carfilzomib with pomalidomide and dexamethasone allowed to achieve complete remission after three cycles of treatment. In this clinical case, we additionally used clarithromycin and metformin to improve the anti-myeloma activity of combination of main treatment. In a brief review of the literature, the frequency of extramedullary lesions, the causes of the appearance of extramedullary lesions, and approaches to diagnosis and therapy are analyzed. Extramedullary lesions with multiple myeloma are a dangerous manifestation of the clonal evolution of the disease, in which the treatment options are still limited, therefore, the demonstration of successful treatment with carfilzomib shows the value of new methods of treatment, as well as the potential effects on the tumor cell when redesigning drug prescriptions