Bone Marrow Multipotent Mesenchymal Stromal Cells from Patients with Aplastic Anemia Retain Their Ability to Support Hematopoietic Precursors despite Pronounced Changes in Gene Expression.

The properties of bone marrow-derived multipotent mesenchymal stromal cells (MSC) of patients with aplastic anemia at the onset of the disease are studied insufficiently. The aim of this work was to test the ability of MSC from patients with aplastic anemia to maintain hematopoietic precursors and to analyze the expression of genes associated with hematopoiesis and immune response. The ability of MSC to maintain hematopoietic precursors was determined by counting cobblestone area-forming cells; gene expression was analyzed by quantitative PCR.

[Detection of activating mutations in RAS/RAF/MEK/ERK and JAK/STAT signaling pathways].

Issue: The study of activating mutations (NRAS,KRAS,FLT3,JAK2,CRLF2genes) of RAS/RAF/MEK/ERK and JAK/STAT signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) in adult patients which are included in Russian multicenter clinical trials.

Materials And Methods: Within the multicenter study there were 119 adult patients included withde novoB-ALL. The study was considered as prospective and retrospective.

Individual Differences of Multipotent Mesenchymal Stromal Cells Manifesting in during Interaction with Lymphocytes.

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.

Co-Culturing of Multipotent Mesenchymal Stromal Cells with Autological and Allogenic Lymphocytes.

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.

[Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009].

Aim: To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells).

Subjects And Methods: The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.

Changing the Properties of Multipotent Mesenchymal Stromal Cells by IFNγ Administration.

We studied changes in the population of human multipotent mesenchymal stromal cells activated by IFNγ. The cells were cultured under standard conditions; IFNγ was added in various concentrations for 4 h or over 2 passages. It was shown that the total cell production significantly decreased after long-term culturing with IFNγ, but 4-h exposure did not affect this parameter.

[Characteristics of stromal cell precursors in patients after allogeneic bone marrow transplantation].

Unlabelled: AIM. To study the elements of the mesenchymal stromal cell compartment (multipotent mesenchymal stromal cells (MMSCs)) and their more mature progenies of fibroblast colony-forming units (CFU-F) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS.

[Effect of bortezomib on the efficiency of hematopoietic stem cell mobilization in patients with multiple myeloma].

Aim: To study the results of mobilizing and collecting autologous hematopoietic stem cells (HSC) in patients with multiple myeloma (MM) receiving bortezomib as part of induction therapy regimens.

Materials And Methods: In June 2001 to April 2010, the Department of Bone Marrow Transplantation, Hematology Research Center, Ministry of Health and Social Development of Russia, mobilized autologous HSC in 93 patients with MM, by using cyclophosphan (CF) and granulocyte colony-stimulating factor. The analysis covered 73 patients who received VAD and/or bortezomib-containing courses as induction therapy.

[Dynamic study of Bcl-2, Bax, p53, and ACE expression in CD34+ cells of peripheral blood and bone marrow in acute leukemia patients in the course of induction chemotherapy].

Aim: To determine unbalance in the system of programmed cell death in the cells CD34+ of the bone marrow (BM) and peripheral blood (PB) before and after cytostatic impact in acute leukemia (AL).

Material And Methods: Flow cytoflowmetry estimated expression of Bcl-2, Bax, p53 and ACE in the cells CD34+ of BM and PB from 10 AL (4 AML and 6 ALL) patients. PB and BM samples were studied before polychemotherapy (PCT) and in the course of induction treatment: on day +8, +21 (blood only), +36 - 38.

[Leukemic dendritic cells in patients with acute myeloid leukemia].

Aim: To determine surface and intracellular expression of ACE antigen and Bip shaperon on leukemic dendritic cells (LDC); to study expression of ACE genes and Bip, Calnexin, calreticulin shaperons in LDC at diagnosis of acute myeloid leukemia (AML) under standard and stress cultivation.

Material And Methods: Expression of ACE antigens and Bip was studied with immunophenotyping and flow cytometry using monoclonal antibodies to shaperon Bip and to CD143), expression of genes of ACE and shaperons Bip, Calnexin, Calreticulin--with polymerase chain reaction (RT-PCR). Dendritic cells (DC) were obtained by culturing of a monoclonal fraction of donor peripheral blood and AML patients in the presence of 180 ng/ml calcium ionophor A23187 (Sigma) for 4 days in parallel at 37 degrees C and 33 degrees C in the atmosphere of 5% CO2.

[Transplantations of allogenic and autologous hemopoietic stem cells in acute leukemia (results of 20-year experience)].

Aim: To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006.

Material And Methods: A total of 71 allogenic and 45 autologous THSC were performed in 116 patients with different AL variants. Conditioning in all allo-THSC included busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg).

[Characteristics of T-cell immunity in patients with acute leukemia].

Aim: To study a cytokine profile of cytotoxic T-cells and T-helpers at diagnosis of acute myeloid and lymphoblastic leukemia (AML and ALL) and at different stages of its treatment.

Material And Methods: T-cell population of peripheral blood lymphocytes was studied in 19 AML patients at diagnosis, 13 AML patients in remission, 5 AML patients in developing recurrence and 5 ALL patients at diagnosis. The control group consisted of 10 healthy donors.

[Superhigh doses of dexamethasone in treatment of refractory forms of acute lymphoblast leukemia of adults].

Aim: Assessment of high-dose dexamethasone efficacy in combination with standard drugs (adriablastin, vincristin, alpha-asparaginase) in patients with refractory acute lymphoblastic leukemia (ALL).

Material And Methods: A pilot multicenter trial with participation of hematological departments of Hematological Research Center (Moscow), municipal hospital N 1 (Krasnoyarsk), municipal hospital N 8 (Yaroslavl), Research Institute of Hematology and Blood Transfusion (Kirov) included 34 patients (10 patients with late recurrences, 24--with primary resistant forms, early and secondary recurrences).

Results: In patients with late ALL recurrences a complete remission (CR) was achieved in 70% cases, the median being 10 months.

[Detection of minimal residual disease in patients with acute myeloid leukemia].

Aim: Detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) and the study of its correlations with duration of recurrence-free interval.

Material And Methods: Bone marrow samples obtained from 37 AML patients before treatment were studied at two-color flow cytometry. The panel of monoclonal antibodies to T- and B-cell, myeloid antigens was used.

[The efficacy of high-dose chemotherapy and the transplantation of autologous hemopoietic cells in lymphogranulomatosis].

Aim: To determine clinical effectiveness of high-dose polychemotherapy (PCT) and transplantation of autologous hemopoietic cells (TAHC) in patients with lymphogranulomatosis (LGM).

Material And Methods: 27 LGM patients aged 16-42 years who have undergone TAHC after high-dose PCT (BEAM--17 patients or CBV--10 patients). 4 patients given high-dose PCT were in the first-second complete remission (CR), 7 patients--in the first partial remission (PR).

[Effectiveness of allogeneic bone marrow transplantation in patients with acute leukemia in complete remission and in patients with chronic myeloid leukemia during the chronic phase].

Aim: To study clinical efficiency of allogenic bone marrow transplantation (ABMT) in patients with acute leukemia (AL) in the first remission and in patients with chronic myeloid leukemia (CML) in chronic phase; to analyse overall and recurrence-free survival in relation to the diagnosis and age.

Materials And Methods: 26 patients with AL and 24 ones with CML (29 males and 21 females) were subjected to ABMT within 10 last years. Median of age in AL and CML was 24.

[A trial of the clinical use of thienam in treating severe and life-threatening suppurative-septic complications].

The authors share their experiences with treatment of 12 patients using the antibiotic Tienam. No complications resulting from the administration of this medicine were noted. High therapeutic efficiency of Tienam has been shown.

[Effect of ketamine anesthesia on patients with severe trauma at the pre-hospital stage on the course and outcome of shock].

Under study were remote results of treatment of patients with critical traumas followed by shock who were given prehospital Ketamine anesthesia. The data obtained were compared with remote results of treatment of patients who did not receive anesthesia at the prehospital stage or who were given narcotic analgetic drugs for anesthesia. Reliable data were obtained showing the course of trauma disease to be more favourable in a group of patients who were given Ketamine anesthesia at the prehospital stage.

[Organization of medical services for patients with severe mechanical trauma].

Analysis of the work of surgical-reanimation teams of the Accident Station and the City Shock Center has shown that their joint activity can provide modern level of giving help to patients with traumatic shock. In organization of work of the City Shock Center of great importance is the distribution of duties among the team members.

[Prognosis of the outcomes in cerebrocranial trauma combined with extracranial injuries complicated by shock].

A method for parametrical prognosis of outcomes of associated cranio-cerebral traumas has been developed on the basis of simple clinical features such as pulse rate, systolic arterial pressure, severity of the trauma expressed in numbers and the level of consciousness. The outcome is prognosticated by the formula obtained as a result of multifactorial regression analysis reliable in 85--90% of cases.