Актуальность. Рак молочной железы (далее РМЖ) сопровождается не только соматическими проявлениями, но и изменениями когнитивного функционирования (память, внимание, речь) и эмоциональной сферы (депрессия, агрессия, враждебность). До начала системного лечения рака могут фиксироваться различные когнитивные дефициты и специфические эмоциональные реакции, которые потенциально оказывают негативное влияние на качество жизни и способность пациенток адаптироваться к болезни. При этом в ходе системной противоопухолевой терапии данные показатели могут усугубляться, снижая комплаентность и создавая помехи участию в реабилитационных мероприятиях. Цель. Изучить взаимосвязь когнитивного функционирования и эмоционального состояния женщин со злокачественными новообразованиями молочных желез до начала системного лечения. Выборка. В исследование вошли 24 пациентки с подтверждённым диагнозом РМЖ без метастазирования (средний возраст 59 ± 12 лет), которые ранее не получали никакого лечения в связи с онкопатологией. Методы. Для выявления когнитивных дефицитов применялась Монреальская шкала когнитивной оценки (MoCa). Уровень агрессии и враждебности определялись опросником агрессивности Басса-Дарки, наличие депрессивных состояний выявляли по шкале Бека. Результаты. У женщин с впервые выявленным РМЖ отмечено зависимое от возраста снижение когнитивных функций, сопряженное с селективным ростом враждебности, тогда как депрессия остается субклинической и лишь ее соматический компонент коррелирует с вербальной агрессией. Выводы. Полученные результаты подчеркивают важность учета когнитивных и эмоциональных характеристик функционирования нервной системы пациенток до начала системной терапии рака, что свидетельствует о необходимости комплексного подхода и проведения дальнейших лонгитюдных клинических исследований для уточнения динамики этих показателей в процессе системного лечения онкопатологии.

АКТУАЛЬНОСТЬ. Минимальная остаточная болезнь (МОБ) — опухолевые клетки, выявляемые высокочувствительными методами (ПЦР, проточная цитометрия) у пациентов в полной ремиссии. Каждый протокол лечения требует определения порогового значения МОБ, т. е. количественного значения лейкозных клеток, которое разделяет пациентов на группы с разным прогнозом. ЦЕЛЬ. Определить пороговое значение МОБ у пациентов с острыми миелоидными лейкозами (ОМЛ), получавших терапию по протоколам «ОМЛ-17» и «mОМЛ-17». МАТЕРИАЛЫ И МЕТОДЫ. В исследование включено 73 пациента с ОМЛ (возраст ≤ 60 лет). МОБ оценивали методом многоцветной проточной цитометрии после 1-го и 2-го курсов индукции. Статистический анализ включал оценку безрецидивной выживаемости по методу Каплана—Мейера, метод ROC-survival для определения порогового значения МОБ. РЕЗУЛЬТАТЫ. Полная ремиссия достигнута у 89,1 % пациентов. МОБ-отрицательный статус после 1-го курса индукции зафиксирован у 66,7 % пациентов, после 2-го курса — у 74,6 %. С помощью анализа ROC-survival установлены пороговые значения МОБ: 0,1 % после 1-го курса индукции и 0,03 % — после 2-го. При пороге 0,1 % 3-летняя общая выживаемость после 1-го курса индукции составила 47,1 % у пациентов с МОБ-положительным статусом vs 96,9 % у пациентов с МОБ-отрицательным статусом, после 2-го курса — 85,8 и 51,8 % соответственно. ЗАКЛЮЧЕНИЕ. Мониторинг МОБ после 1-го и 2-го курсов индукционной терапии по протоколам «ОМЛ-17» и «mОМЛ-17» позволяет выделить группу пациентов с высоким риском развития рецидивов. Критическими пороговыми значениями МОБ являются 0,1 % после 1-го курса индукции и 0,03 % — после 2-го.

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms provides the knowledge basis for decision making in diagnosis, therapy, prevention, and rehabilitation in compliance with evidence-based medicine principles in order to ensure appropriate medical care in a particular clinical setting. The clinical guidelines underly the choice of optimal methods of diagnosis, therapy, prevention, and rehabilitation as part of a patient’s medical care, the development of criteria for the assessment of medical care quality, medical care standards, medical care procedures, setting standards on equipment and management of diagnostic and therapeutic procedures, and provision of continuous medical education and advanced training for healthcare professionals. In 2013, a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context, clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who are directly involved in treatment activities. The present edition is an upgraded version of clinical guidelines with updated information on classification, diagnosis, prognosis, current methods of therapy, and their efficacy and tolerability assessment. The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

Aim. To identify the characteristics of T-helper subpopulations in healthy donors and to compare them with those reported in acute leukemia patients 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The study enrolled 41 blood donors and 49 patients after-HSCT. The median age of donors was 36 years (range 20–60 years), 29 of them were men and 12 were women. The median age of patients was 37 years (range 19–62 years), 18 of them were men and 31 were women. Acute myeloid leukemia was diagnosed in 27 (55 %) patients and acute lymphoblastic leukemia/lymphoma in 22 (45 %) patients. Myeloablative conditioning was administered to 4 (8 %) patients and reduced intensity conditioning to 45 (92 %) patients. T-helper subpopulations were studied in the blood of healthy donors vs. acute leukemia patients after allo-HSCT. The flow cytometry analysis was conducted to simultaneously assess the expression of markers CD3, CD4, CD8, CD25, CD45RA, CD197, CD28, CCR4, CCR6, CCR10, CXCR3, and CXCR5 in T-cells. Results. The study demonstrated that the count of T-helpers at different stages of differentiation (regulatory, naive T-cells, memory cells, and effector cells) comprehensively distinguishes healthy donors from patients. Moreover, the functional structure of each of these populations differ in donors vs. patients even on Month +6 after allo-HSCT. Donors appeared to have more polarized cells among the central memory T-helpers. The proportion of T-helpers type 1 among the effector cells was higher is patients. Conclusion. The results of the study indicate that the Т-cell parameter set can be analyzed to assess immunity and to describe its disorders in different pathologies or after drug chemotherapy.

Introduction. Syngeneic hematopoietic stem cell transplantation is a type of allogeneic stem cell transplantation when the donor of stem cells is a genetically identical (monozygotic) twin of the recipient. After this type of transplantation, there is no immunological conflict as the graft versus host disease, but at the same time, there is no positive effect of the graft-versus-leukemia effect. Aim: to assess the overall survival, event-free survival, probability of relapse, and transplant-related mortality rates associated with syngeneic stem cell transplantation. Patients and methods. In the National Research Center for Hematology from January 1988 to December 2018 we performed 654 allo-HSCT: 17 (2.5%) of them from a syngeneic donor. We performed a «paired analysis» with patients after allo-HSCT from a HLA-identical sibling donor. We included patients after allo-HSCT from an HLA-identical related donor (n = 28) in Group 1 and patients after syngeneic stem cell transplantation in group 2 (n = 14). Patients with aplastic anemia (n = 3) were excluded from the «paired analysis». Results. Patients after syngeneic stem cell transplantation did not develop a graft-versus-host disease. The relapse developed in 50% of cases (n = 7). Five patients (35.7%) died: 4 of them due to the relapse of the disease, and 1 - due to the graft failure. The relapse probability in patients after syngeneic HSCT was higher and amounted to 18.4% versus 54.2% (p = 0.047) for allo-HSCT from HLA-identical sibling donor and a syngeneic donor, respectively. Overall and event-free survival in patients after syngeneic HSCT is comparable to those in patients after allo-HSCT from an HLA-identical sibling donor. Conclusion. Syngeneic hematopoietic stem cell transplantation is justified in the absence of another related or unrelated donor of hematopoietic stem cells. The use of myeloablative conditioning regimens, peripheral blood stem cells as a source of stem cells, or high doses of nucleated cells/kg in the case of using bone marrow will improve post-transplant parameters in patients after syngeneic hematopoietic stem cell transplantation.

Multipotent mesenchymal stromal cells (MSC) were administered to patients after allogeneic hematopoietic stem cell transplantation to prevent the development of acute graft—versus— host disease (GVHD). The injection of MSC did not always prevent the development of GVHD. The aim of the work was to compare the secretome of MSC effective and ineffective in the prevention of GVHD. MSC were obtained from the bone marrow of hematopoietic stem cells donors. The secretome was studied using a TripleTOF 5600+ mass spectrometer with a NanoSpray III ion source coupled to a NanoLC Ultra 2D Plus nano-HPLC System. A total of 1,965 proteins were analyzed. Analysis of the secretome of effective and ineffective MSC samples revealed significant differences in the secretion of 1,119 proteins associated with ribosomes, exosomes, focal contacts, and others. Analysis of proteins secreted by MSC can be used to identify prognostically effective samples.

Introduction . Primary myelofibrosis (PMF) is a clonal disease violating the cell composition, histological topography and stroma in bone marrow (BM). Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy in PMF. Aim  — description of change in the haematopoietic tissue cell composition and stroma, as well as in trabecular bone in allo-HSCT patients with fibrotic PMF. Materials and methods . We studies 24 trephine biopsy samples from nine PMF patients with allo-HSCT at the intervals: I — 1 month prior to, II — past 1–3 months and III — past 4–6 months from allo-HSCT. BM trephine biopsy slides were prepared in a standard histological assay with haematoxylin—eosin and additional staining with Gomori’s silver and Masson’s trichrome. Morphological change was evaluated in reticulin and collagen stroma, bone trabeculae, cellularity and topography of haematopoietic tissue. Results . The BM trephine biopsies of interval I were morphologically distinguished in three types by haematopoietic cellularity, stromal and trabecular sclerotic change. Post-transplant intervals II and III (3–6 months after allo-HSCT) did not reveal these types but showed an evident myelofibrosis and osteosclerosis reduction and signs of a restoring bone remodelling cycle. Myelopoietic lineages recovered in stages: the erythroid germ restored in three, granulocytic — in six months, and megakaryocytic cellularity did not fully recover in six months. Myelopoietic cellularity recovery outpaced blood recovery, which may be due to induced myelodysplasia or disruption of stromal niches. Conclusion . Allo-HSCT leads to the disappearance of PMF-pathognomonic BM morphology reflecting a histological remission. The reduction of myelofibrosis and osteosclerosis and normalisation of the trabecular bone remodelling cycle in post-transplant periods indicates an impact of cell microenvironment on PMF pathogenesis and warrants research into the composition and histological topography of cell microenvironment in PMF.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a standard treatment for many patients with hematological malignancies. Over the past 20 years, an increase in transplantation activity has been noted throughout the world. About 50 % of all allo-HSCT are transplanted from unrelated donors. Aim: to present the dynamics and stages of the development of unrelated donation using the example of one transplant center. Materials and methods. This study analyzed Allo-HSCT performed from 2009 to March 2019 at the National Research Center for Hematology (NRCH). The work of the unrelated donor recruiting group and the tissue typing laboratory was analyzed for this period. 107 patient requests for unrelated donor search were dissected to identify search failures. The parameters of 206 unrelated donors were estimated depending on the register (Russian Federation/foreign). Results. The number of allo-HSCTs did not exceed more than 20 per year, in 2009–2011. Since 2012, the number of alloHSCT signifi cantly increased when the possibility for searching for unrelated donors abroad as well as in the Russian Federation (RF) databases appeared. During this time an increase by more than 50 % was noted in the number of allo-HSCTs. Allo-HSCs from unrelated donors of the Russian Federation make up 30–40 % of all unrelated allo-HSCs. 16 % of potential donors of hematopoietic stem cells included in the NRCH registry are donors of the human blood components. Despite the increasing number of unrelated donors in international and RF databases, 12 % of patients did not fi nd a compatible donor in any of the registers, due to a rare combination of HLA genes. It was revealed that among donors from the RF from whom alloHSCT was performed, there was not a signifi cant prevalence of men, compared to the foreign registry, 50.7 % and 66.7 %, respectively, despite the preference of donor-male by doctors. The 5-year overall survival in patients with acute leukemia in the fi rst complete remission, depending on the performance of allo-HSCT from a donor from the RF or foreign registers, are comparable, 40 % and 39.5 %, respectively. Conclusion. The number of allo-HSCT has increased 5 times over the past 10 years largely due to the development of unrelated donation: 30–40 % of allo-HSC transplants received from unrelated donors were performed from donors from the United database of the Russian Federation. The 5-year overall survival of these patients is comparable with the results of the overall survival patients who received transplants from donors from foreign registers.

Background and Objectives Bone marrow transplantation with umbilical cord blood (UCB) in adult recipients is limited mainly by a low CD34 + cell dose. To overcome this shortcoming by minimum manipulation, mineralized bone allograft (MBA) scaffold coated by UCB-USSC (unrestricted somatic stem cells) was used to expand CD34 + cells from UCB. Materials and Methods In this experimental study, UCB-USSCs were isolated and characterized by morphologic and immunophenotypical analysis. Then they were seeded on MBA (for 3D figuration) and culture plate (for 2D figuration) as a feeder layer. CD34 + cells were isolated from the UCB (by MACS method) and were expanded in 2D and 3D conditions for 3 weeks. At the end, cell count, flow cytometry, cologenic assay, and LTC-IC were done. Results After 3 weeks, ex vivo expansion of UCB-CD34 + was enhanced 250 ± 13.2 in 3D. The highest CFC expansion and LTC-IC were observed at day 14. Flow cytometry analysis showed the lowest percentage in 3D culture. Conclusions USSCs by 3D MBA structure produce the hematopoietic cytokine, extracellular matrix and binding molecules; they also create the intercellular interaction that can be used as a suitable feeder layer. It provides an ex vivo mimicry of bone marrow niche by enhancing surface/volume ratio. This model could be a suitable and alternative environment for HSCs expansion and hematopoiesis.

Analysis of changes in lymphocyte subpopulations during co-culturing with multipotent mesenchymal stromal cells (MSC) revealed two distinct MSC groups: one group (A) increased HLA-DR expression on lymphocytes during co-culturing and the other (B) did not change it in comparison with lymphocyte monoculture. In stromal cells interacting with lymphocytes, expression of HLA-DR molecules was initiated, but only in samples that induced enhanced expression on lymphocytes and irrespectively of whether allogeneic or autologous lymphocytes were used for co-culturing with MSC. In group A, the relative expression of IDO1 significantly increased in comparison with group B. The revealed individual differences in MSC can explain why not all MSC samples are effective in the treatment of autoimmune diseases, acute "graft-versus-host" disease, and other pathologies.

We studied the effect of autologous and allogeneic lymphocytes on multipotent mesenchymal stromal cells in co-culture. It is shown that changes in multipotent mesenchymal stromal cells and in lymphocytes did not depend on the source of lymphocytes. Contact with lymphocytes triggers expression of HLA-DR molecules on multipotent mesenchymal stromal cells and these cells lose their immune privilege. In multipotent mesenchymal stromal cells, the relative level of expression of factors involved in immunomodulation (IDO1, PTGES, and IL-6) and expression of adhesion molecule ICAM1 increased, while expression of genes involved in the differentiation of multipotent mesenchymal stromal cells remained unchanged. Priming of multipotent mesenchymal stromal cells with IFN did not affect these changes. In turn, lymphocytes underwent activation, expression of HLA-DR increased, subpopulation composition of lymphocytes changed towards the increase in the content of naïve T cells. These findings are important for cell therapy.