22 results on '"Svetlana Kozlovskaya"'
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2. Retraction Note: Impact of digital game-based learning on the social competence and behavior of preschoolers
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Menglin Fang, Olga Tapalova, Nadezhda Zhiyenbayeva, and Svetlana Kozlovskaya
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Library and Information Sciences ,Education - Published
- 2023
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3. Targeted therapy with venetoclax and daratumumab as part of HSCT preparative regimen in children with chemorefractory acute myeloid leukemia.: venetoclax and daratumumab as part of HSCT preparative regimen for AD AML
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Maria, Klimentova, Larisa, Shelikhova, Maria, Ilushina, Svetlana, Kozlovskaya, Sergei, Blagov, Alexander, Popov, Svetlana, Kashpor, Maria, Fadeeva, Julia, Olshanskaya, Svetlana, Glushkova, Dmitriy, Pershin, Dmitriy, Balashov, Alexei, Maschan, and Michael, Maschan
- Abstract
The long-term outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in chemorefractory acute myeloid leukemia (AML) remains suboptimal due to a high relapse rate. Enhancement of conditioning regimens by the incorporation of targeted anti-leukemia agents is a potential approach to improve the efficacy of HSCT. In a pilot trial and extended access cohort, we evaluated the safety and potential value of adding combinations of venetoclax and daratumumab to a preparative regimen among children with chemorefractory acute myeloid leukemia grafted with αβ T-cell-depleted peripheral blood stem cells. All 20 patients had active disease (AD) status of AML at the time of transplantation. The preparative regimen included myeloablative conditioning based on either total body irradiation or treosulfan. A haploidentical related donor was used as a graft source for all patients. Engraftment was not compromised, and no excess toxicity was noted. MRD-negative complete remission was achieved in 17 patients (85%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 17%, and the cumulative incidence of chronic GVHD was 7%. At 2 years, nonrelapse mortality was 10%, relapse incidence was 46%, event-free survival was 44%, and overall survival was 65%. Our data show the possibility of safely adding targeted agents to conditioning regimens; however, no evidence of a significant improvement in long-term transplantation outcomes in this cohort of patients was observed.
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- 2022
4. Features of self-actualization and self-efficacy of students at the university
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Daria Kozlovskaya and Svetlana Kozlovskaya
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General Medicine - Published
- 2022
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5. EFFICACY OF HEMATOPOIETIC STEM CELL TRANSPLANTATION FROM AN ALTERNATIVE DONOR ON THE PLATFORM OF TRANSPLANT CELL MODELING TECHNOLOGY IN PATIENTS WITH PRIMARY IMMUNODEFICIENCIES
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Svetlana Radygina, I.P. Shipitsyna, G.A. Novichkova, Anna Livshits, Alexandra Laberko, Kirill Voronin, Dmitry Balashov, Yu.V. Skvortsova, A.Yu. Shcherbina, Larisa Shelikhova, Svetlana Kozlovskaya, M.A. Maschan, and Immunology named after Dmitry Rogachev, Moscow, Russia
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,In patient ,Hematopoietic stem cell transplantation ,Alternative donor ,business ,Transplant cell - Published
- 2020
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6. Targeted Therapy With Venetoclax and Daratumumab as Part of HSCT Preparative Regimen in Children With Chemorefractory Acute Myeloid Leukemia
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Maria Klimentova, Larisa Shelikhova, Maria Ilushina, Svetlana Kozlovskaya, Sergei Blagov, Alexander Popov, Svetlana Kashpor, Maria Fadeeva, Julia Olshanskaya, Svetlana Glushkova, Dmitriy Pershin, Dmitriy Balashov, Alexei Maschan, and Michael Maschan
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
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7. Socio-pedagogical conditions affecting the professional self-determination of schoolchildren in the changing world of professions
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Angelina Kvitkovskaya, Daria Kozlovskaya, and Svetlana Kozlovskaya
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General Medicine - Published
- 2021
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8. Patriotic tourism as a means education and upbringing of young people
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Daria Kozlovskaya and Svetlana Kozlovskaya
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General Medicine - Published
- 2021
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9. Evaluation of abatacept for GVHD prophylaxis in patients with non-malignant diseases after hematopoietic stem cell transplantation
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I.P. Shipitsyna, Svetlana Kozlovskaya, Larisa Shelikhova, E. I. Gutovskaya, Svetlana Radygina, Anna Livshits, A. P. Vasilieva, and Dmitry Balashov
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Abatacept ,Immunology ,chemical and pharmacologic phenomena ,Non malignant ,Hematology ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,surgical procedures, operative ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Immunology and Allergy ,Gvhd prophylaxis ,In patient ,business ,030215 immunology ,medicine.drug - Abstract
Graft-versus-host diseases (GVHD) is one of most significant complication after allogeneic hematopoietic stem cells transplantation (HSCT). T-cell activation is a major stage in the GVHD pathogenesis. T-cells require 2 signals for activation: cognate antigen/MHC binding T-cell receptors and positive costimulatory signals from antigen-presenting cells (APC). The predominant positive costimulatory signal to human CD4 T0-cells comes through the CD28 receptor. This signal can be blocked by fusion proteins (such as CTLA4-Ig). Abatacept is a soluble fusion protein, which links the extracellular domain of human CTLA-4 to the modified Fc portion of human IgG1. We present results of single-center prospective randomized study to evaluate the efficacy of adding abatacept to the GVHD prophylaxis protocol after hemopoietic stem cell transplantation in patients with non-malignant diseases. Study was approved by Ethics Committee and Scientific Council of the Institute (protocol # 9/2013 from 01.10.2013). During 4 years we included 62 patients, 30 of them received abatacept as additional agent. Cumulative incidence of acute GVHD was significantly lower in this group in compare with control group (p = 0,018). When we stratified patients in dependents of graft processing technology, we did not see any advantages of abatacept in patients after transplantation with TCRαβ+/СD19+ graft depletion. However, after HSCT with non-manipulated graft the abatacept showed significant efficacy in aGVHD prophylaxis compared with control group (p = 0,024). Abatacept can be recommended as effective additional agent for GVHD prophylaxis after allogeneic HSCT in patients with non-malignant diseases.
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- 2019
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10. SUCCESS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR WISKOTT–ALDRICH SYNDROME
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Svetlana Radygina, D.N. Balashov, Larisa Shelikhova, Alexandra Laberko, Yu.A. Rodina, Elvira Sultanova, A.Yu. Shcherbina, Alexey Maschan, Svetlana Kozlovskaya, and Immunology named after Dmitry Rogachev, Moscow, Russia
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Wiskott–Aldrich syndrome ,business.industry ,medicine.medical_treatment ,Pediatrics, Perinatology and Child Health ,Immunology ,medicine ,Hematopoietic stem cell transplantation ,medicine.disease ,business - Published
- 2019
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11. Impact of Digital Game-Based Learning on the Social Competence and Behavior of Pre-Schoolers
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Menglin Fang, Olga Tapalova, Nadezhda Zhiyenbayeva, and Svetlana Kozlovskaya
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Digital gaming has become a regular part of life for today’s pre-schoolers. Hence, there is a need to look at the integration of digital technology into the preschool education. The present study aims to examine the effect digital games have on children's behaviour and their social competence if played to reach an educational purpose (supervised play) and for fun (without educational aim). The study population consists of 54 pre-schoolers (26 girls and 28 boys), aged 4 to 6, who were recruited in Moscow, Russia. All children were divided in two groups: children playing digital games with peers (n = 28) and children playing digital games at home (n = 28). Findings revealed a higher level of social competence in the experimental group (+11.71, p ˂ 0.05) as compared to children playing without being told what they were expected to achieve. The experimental group also scored lower on Anxiety-Withdrawal (-7.94, p ˂ 0.05). A higher Anxiety-Withdrawal score normally means that a child experiences some degree of depression or anxiety, and exhibits overly dependent behaviour. The results of this study may help parents and teachers to use digital learning tools, in particular video games, effectively when working with young children.
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- 2021
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12. A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRαβ+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott-Aldrich Syndrome
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Michael Maschan, Alexander Rumiantsev, Dmitrii S. Abramov, Svetlana Kozlovskaya, Elena Gutovskaya, Dmitry Balashov, Anna Shcherbina, Pavel Trakhtman, Alexandra Laberko, Galina Novichkova, Alexei Maschan, and Larisa Shelikhova
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Transplantation ,medicine.medical_specialty ,Chemotherapy ,Myeloid ,business.industry ,Wiskott–Aldrich syndrome ,medicine.medical_treatment ,Plerixafor ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Stem cell ,business ,030215 immunology ,Whole blood ,medicine.drug - Abstract
Our initial experience with hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD; n=12) or a haploidentical related donor (n = 6) with T cell receptor (TCR)αβ+/CD19+ graft depletion in patients with Wiskott-Aldrich syndrome (WAS) (n = 18) showed a dramatic decrease in the incidence of graft-versus-host disease (GVHD) and transplantation-related mortality, with an increased overall survival (OS) of 88.9%. Unfortunately, the treatment was associated with mixed myeloid donor chimerism and secondary graft dysfunction (severe thrombocytopenia, n=2; graft rejection, n=5). To improve the outcome, we hypothesized that the addition of G-CSF and plerixafor to the conditioning chemotherapy would result in more complete donor stem cell engraftment. This trial was registered at www.clinicaltrials.gov (NCT03019809). A study group of patients with WAS (n = 16) underwent TCRαβ+/CD19+-depleted HSCT (MUD, n=6; haploidentical, n=10). The conditioning regimen was treosulfan-fludarabine-rabbit antithymocyte globulin-melphalan (or thiophosphamide in 1 patient) with G-CSF (10 µg/kg/day for 5 days starting on day −8) and plerixafor (240 µg/kg/day for 3 days starting on day −6). The clinical outcomes in this study were compared to those in a historical dataset (n = 18). No patients had grade III/IV acute GVHD in either the study or the historical control group. Importantly, in the patients with WAS, there was no statistical significance in OS between those who underwent HSCT from haploidentical donors and those who underwent HSCT from MUDs (93.8% versus 88.5%; P = .612). All patients in the study group had full donor chimerism in whole blood and in the CD3+ compartments. The OS was 93.8%, and there were no cases of graft dysfunction. This study demonstrates the efficacy of adding G-CSF/plerixafor to the conditioning regimen before HSCT with TCRαβ+/C D19+ graft depletion in patients with WAS.
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- 2018
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13. Posttransplant lymphoproliferative disorder in children after allogeneic hematopoietic stem cell transplantation: a single-center experience and literature review
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Andrej B. Abrosimov, Yurij A. Krivolapov, E V Skorobogatova, Elena Samochatova, Irina Shipitsina, Irina Kalinina, Galina V. Tereshenko, Dmitrij M. Konovalov, Michael Maschan, Alexej A. Maschan, Svetlana Kozlovskaya, Y.V. Skvortsova, Larisa Shelikhova, Elena Gutovskaya, Alexander Rumyantsev, Dina D. Bajdildina, Ulyana N. Petrova, Galina Novichkova, Dmitrij S. Abramov, and D.N. Balashov
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Oncology ,Transplantation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Internal medicine ,Molecular Medicine ,Medicine ,Hematopoietic stem cell transplantation ,business ,Single Center - Published
- 2017
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14. The use of plerixafor and g-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome
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E.I. Gutovskaya, A.L. Laberko, Svetlana Radygina, Svetlana Kozlovskaya, A.A. Maschan, and Dmitriy Balashov
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Oncology ,medicine.medical_specialty ,business.industry ,Plerixafor ,medicine.medical_treatment ,Immunology ,Hematology ,Hematopoietic stem cell transplantation ,Internal medicine ,Pediatrics, Perinatology and Child Health ,ALDRICH SYNDROME ,Immunology and Allergy ,Medicine ,business ,medicine.drug - Published
- 2017
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15. A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRαβ
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Dmitry, Balashov, Alexandra, Laberko, Anna, Shcherbina, Pavel, Trakhtman, Dmitrii, Abramov, Elena, Gutovskaya, Svetlana, Kozlovskaya, Larisa, Shelikhova, Galina, Novichkova, Michael, Maschan, Alexander, Rumiantsev, and Alexei, Maschan
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Male ,Benzylamines ,Transplantation Conditioning ,Anti-HIV Agents ,Receptors, Antigen, T-Cell, alpha-beta ,Antigens, CD19 ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,Infant ,Cyclams ,Wiskott-Aldrich Syndrome ,Treatment Outcome ,Heterocyclic Compounds ,Child, Preschool ,Humans ,Female ,Child - Abstract
Our initial experience with hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD; n = 12) or a haploidentical related donor (n = 6) with T cell receptor (TCR)αβ
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- 2018
16. Professiogram social worker
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Svetlana Kozlovskaya
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Emotional labor ,Social work ,Demographic economics ,Psychology - Published
- 2017
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17. Theory and practice of development of professional self-determination of students
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Svetlana Kozlovskaya
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- 2016
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18. Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen in Patients with Wiskott-Aldrich Syndrome Given Allogeneic Hematopoietic Cell Transplantation — an EBMT Inborn Errors Working Party and Scetide Retrospective Analysis
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Junfeng Wang, Christoph Klein, Karl-Walter Sykora, Marco Zecca, Tatjana A Bykova, Krzysztof Kałwak, Nizar Mahlaoui, Paul Veys, Maria Ester Bernardo, Ekrem Unal, Mary Slatter, Michael H. Albert, Ivana Bodova, Andrew R. Gennery, Despina Moshous, Fulvio Porta, Henric-Jan Blok, Ansgar Schulz, Alain Fischer, Robert Chiesa, Benedicte Neven, Svetlana Kozlovskaya, Jacek Winiarski, Virginie Courteille, Tayfun Guengoer, Renata Formankova, O. Alphan Kupesiz, Bénédicte Bruno, Arjan C. Lankester, and Franco Locatelli
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Oncology ,medicine.medical_specialty ,Cyclophosphamide ,Wiskott–Aldrich syndrome ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,ThioTEPA ,Treosulfan ,medicine.disease ,Biochemistry ,Fludarabine ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,Busulfan ,030215 immunology ,medicine.drug - Abstract
PV and AL contributed equally Multiple studies from the EBMT registry and others have shown excellent survival rates after allogeneic haematopoietic stem cell transplantation (HSCT)for Wiskott-Aldrich syndrome (WAS) patients (Ozsahin et al, Blood 2008). The importance of myeloid engraftment for full disease correction has also been demonstrated (Moratto et al, Blood 2011). However, the vast majority of HSCTs in these studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. In 2005, the inborn errors working party (IEWP) of EBMT and ESID first recommended busulfan/fludarabine (BuFlu) or treosulfan/fludarabine (TreoFlu) based conditioning for primary immunodeficiencies such as WAS, with some centers deciding to add thiotepa (TT) to the conditioning. We performed a retrospective analysis via the EBMT and SCETIDE registries of WAS patients transplanted between 01/01/20006 and 12/31/2016 with these two regimens. The primary objective was to compare the overall (OS) and event-free survival (EFS) after HSCT with either BuFlu±TT or TreoFlu±TT conditioning. Secondary objectives included the influence of either conditioning regimen on acute and chronic GVHD, the degree of donor chimerism, incidence of secondary procedures after HSCT (2nd HSCT, stem cell boost, DLI, gene therapy or splenectomy) and rates of disease-specific complications after HSCT. At the time of this interim analysis, 174 patients were included, 92 (53%) with BuFlu±TT and 82 (47%) with TreoFlu±TT conditioning with a median age of 1.57 years (range 0.21-29.96) at HSCT and a median follow-up of 32.9 months (range 1.5-128.9). The donor was an HLA-matched sibling (MSD) in 30, a matched related donor (MRD) in 5, a matched unrelated donor (MUD, 9/10 or 10/10) in 105, a mismatched unrelated donor (MMUD, 5 years had a worse OS as compared to those 5 years or younger at HSCT (74.9% vs. 90.8%; log-rank test p=0.005). The type of donor had no influence on OS: 96.4% for MSD/MFD, 86.8% for MUD/MMUD and 87.7% for MMFD (log-rank test p=0.4). Whole blood chimerism was complete (>90% donor) in 60/75 evaluable patients (80%) at last follow-up or before secondary procedure (if a patient had one), 39/40 (98%) in the BuFlu±TT group and 21/35 (60%) in the TreoFlu±TT group. Twenty-six patients required a secondary procedure: stem cell boost in 4 patients, donor lymphocyte infusion in 9, 2nd HSCT in 15 and splenectomy in 1. Twenty-two of these 26 (84.6%) are alive and 14 of 16 with available chimerism data have a complete donor chimerism (>90%donor) at last follow-up. The 2-year cumulative incidence (CI) of secondary procedures was higher at 33.9% in the TreoFlu±TT versus 12.8% in the BuFlu±TT group (Gray's test p=0.017), and 2-year EFS (secondary procedure or death as event) was 61.4% in the TreoFlu±TT and 75.0% in the BuFlu±TT group (log-rank test p=0.2). Grade II-IV acute GVHD had the same incidence in both groups (100 day CI 24.4% vs. 26.3%; Gray's test p=0.849) and chronic GVHD of any grade was borderline more frequent in the TreoFlu±TT group (2 year CI 17.2% vs 6.7%; Gray's test p=0.054). The cumulative incidence of disease-specific complications occurring more than 6 months post HSCT (severe infections, bleeding, autoimmunity) was not different between the two groups (6.5% vs. 6.4%; Gray's test p=0.92). There was no malignancy reported after HSCT except for one EBV-post-transplant lymphoproliferative disorder (PTLD) 2.7 months after HSCT. In summary, HSCT with either BuFlu±TT or TreoFlu±TT conditioning reliably cures almost 90% of patients with WAS regardless of donor type. WAS-related complications are very rare events more than 6 months post HSCT. More patients required secondary procedures after treosulfan-based than busulfan-based conditioning. These data confirm the feasibility and efficacy of the regimens currently recommended by the IEWP. Disclosures Slatter: Medac: Other: Travel assistance. Chiesa:Gilead: Consultancy; Bluebird Bio: Consultancy. Kalwak:Sanofi: Other: travel grants; medac: Other: travel grants. Locatelli:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria.
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- 2018
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19. Replacement of Polyclonal Anti-Thymocyte Globulin By Targeted Immunomodulation Is Associated with Improved Outcome of Alfa\Beta T Cell-Depleted Hematopoietic Stem Cells Transplantation in Children with Acute Leukemia
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Elena Kurnikova, Irina Shipitsina, Maria Fadeeva, Anna Bogoyavlenskaya, Svetlana Kozlovskaya, Dmitriy Pershin, Michael Maschan, Dmitriy Balashov, Maria Ilushina, Alexey Nechesnyuk, Elena Gutovskaya, Yakov Muzalevsky, Yulia Olshanskaya, Dmitry Litvinov, Zhanna Shekhovtsova, Alexey Maschan, Alexey Kazachenok, Sergey Blagov, Galina Novichkova, Rimma Khismatullina, Natalia Miakova, Irina Kalinina, Daria Shasheleva, and Larisa Shelikhova
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medicine.medical_specialty ,Acute leukemia ,Thymoglobulin ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Anti-thymocyte globulin ,Transplantation ,Graft-versus-host disease ,Internal medicine ,Lymphocyte costimulation ,medicine ,Cumulative incidence ,business - Abstract
Introduction Relapse, graft-versus-host disease (GvHD) and associated non-relapse mortality are the main obstacles to successful hematopoietic stem cell transplantation in children with leukemia. αβ T cell depletion was developed to prevent GvHD and improve immune reconstitution in recipients of mismatched grafts. Most current protocols use rabbit anti-thymocyte globulin (ATG) as an essential component of preparative regimen to secure engraftment and GVHD control. In order to avoid damaging effects of circulating ATG on graft NK and gd T cells, we have replaced ATG with pharmacologic blockade of IL-6 and CD80/CD28 co-stimulation axis in our ongoing study. Patients and methods Major transplantation outcomes were compared between participants of the current prospective trial (ATG-) and a retrospective control group (ATG+). A total of 165 children with acute leukemia (67 AML, 98 ALL, 68 female, 97 male, median age 8,7 y) underwent allo HSCT between 01.11.2013 and 01.03.2018. Of them 134 - from haploidentical donor and 31 from unrelated donor. All pts were in complete remission (CR1=80, CR2=67, CR>2=18). Ninety-two pts received treosulfan-based conditioning, 73 - TBI-based (all ALL). Either melphalan (n=46) or thiophosphamide (n=98) or etoposide (n=21) were added as a second agent. Fludarabine was used in all pts. Two types of GVHD prophylaxis were used: type 1 (ATG+), (n=98): thymoglobulin 5mg/kg, rituximab 200mg/m2 with either bortezomib on days +2, +5 (n=72) or tacro (n=9) or without any additional agents (n=17); Type 2 (ATG-) (n=67): tocilizumab at 8 mg/kg on day -1, bortezomib on day +2, +5 with abatacept at 10 mg/kg on day -1, +7, +14, +28 (n=63) or without added agent (n=4). αβ T cell depletion with CliniMACS was used in all cases. The median dose of CD34+ cells was 9x106/kg, αβ T cells - 16 x103/kg. Modified (CD45RA-depleted) donor lymphocyte infusions (DLI) were administered to 113 pts. Twenty-five patients received DLI on day 0 and 88 pts received DLI after engraftment. Median time of follow-up for survivors was 2 years (range, 0,3 - 4,5). Results Three patients died before engraftment due to septic event. Primary engraftment was achieved in 161 of 162 evaluable pts (99,3%), the median time to neutrophil and platelet recovery was 16 and 15 days. Among the whole cohort the cumulative incidence of acute graft-versus-host disease (GvHD) grades II - IV and III - IV was 11,5% (95% CI: 7,5-17,6) and 4,8% (95% CI: 2,5-9,5) respectively. The cumulative incidence of cGvHD was 10 % (95% CI: 6,3-15,9). The incidence of aGvHD and cGvHD was not different between ATG (+) and ATG (-). Among the whole cohort 2-year pTRM was 8% (95%CI: 4,8-13,5). pTRM was significantly lower among ATG (-) group - 1,5% (95%CI:0,2-10,4) versus 12,2% (95%CI:7,2-20,8) among ATG (+) group, p = 0,015. The cumulative incidence of relapse at 2 years was 21% (95%CI: 15,5-29), 24% (95%CI: 16-35), among ATG (+) and 19% (95%CI: 11-32), among ATG (-), p = 0,8. Two-year pEFS was 70% (95%CI: 62-77), 2-year pOS - 78% (95%CI: 71-85). Among patients, who received ATG (-) regimen, pEFS was 76% (95%CI: 68-89), as compared to 65% (95%CI: 56-75) among ATG (+), p=0,1 and pOS was 89% (95%CI: 81-97) versus 72% (95%CI: 63-81), p=0,032, respectively. αβ T cell recovery at day +30 was associated with a trend to decreased incidence of relapse, CI of relapse was 32% (95% CI:22 - 47) in those with αβ-T cell count < median vs 18 % (95% CI: 11-32) in those with αβ-cell count >median, p=0,08. EFS among αβ T" high" was 81% (+/-10) vs 56% (+/-14) among αβ T"low", p=0,002. Discussion We confirm that the depletion of αβ T cells from the unrelated and haploidentical graft in combination with intensive conditioning regimen ensures high engraftment rate and low transplant-related mortality. Our analysis suggests that polyclonal ATG serotherapy is not an essential part of the transplant regimen in αβ T-depleted transplantation. Combined administration of tocilizumab and abatacept after αβ T cell-depleted grafting effectively prevents GVHD, does not compromise engraftment, appears to decrease non-relapse mortality and improve survival. Disclosures No relevant conflicts of interest to declare.
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- 2018
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20. Targeting Bcl-2 and CD38 As Part of Personalized HSCT Conditioning Regimen in Chemorefractory Pediatric Leukemia
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Maria Alyabeva, Larisa Shelikhova, Daria Shasheleva, Rimma Khismatullina, Svetlana Radygina, Anna Bogoyavlenskaya, Sergey Blagov, Olga Molostova, Svetlana Kozlovskaya, Irina Kalinina, Elena Kurnikova, Yakov Muzalevsky, Dmitriy Pershin, Alexander Popov, Olga Illarionova, Yulia Olshanskaya, Natalia Miakova, Dmitry Litvinov, Galina Novichkova, Alexey A. Maschan, and Michael Maschan
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Oncology ,Acute leukemia ,medicine.medical_specialty ,Childhood leukemia ,Juvenile myelomonocytic leukemia ,business.industry ,Venetoclax ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Transplantation ,Leukemia ,chemistry.chemical_compound ,chemistry ,Median follow-up ,Internal medicine ,Medicine ,business - Abstract
Introduction The outcome hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity. We hypothesized that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic hematopoietic stem cell transplantation in a cohort of pediatric patients with refractory leukemia. Bcl-2 and CD38 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies, venetoclax and daratumumab, and expected non-overlapping toxicity profile of these agents and the conditioning regimen. Materials and methods A total of 16 pts with chemorefractory disease (T-ALL - 2, AML - 8, JMML - 6, 12 male, 4 female, median age 5,7 years), underwent HSCT between November 2017 and June 2018, median follow-up - 3 months (1,6-7). All pts were transplanted from haploidentical donors, had active disease (AD) at the moment of SCT, for 12 (75%) pts it was the first allogenic HSCT, for 4 pts it was the second HSCT. Median bone marrow leukemia burden before cytoreduction was 22% (3-75). Bcl-2 expression on the tumor cells was detected in all pts (100%) with the median expression of 69% (0,7-100), CD38 expression was detected in 10 pts (AML=7, ALL=2, JMML-1) with the median expression of 96% (71-100). Ten pts received treosulfan-based conditioning, 3 - busulfan-based and 3 -TBI-based. GVHD prophylaxis included tocilizumab at 8 mg/kg on day -1, post-transplant bortezomib and abatacept at 10 mg/kg on day -1, +7, +14, +28. Three pts received thymoglobulin 5mg\kg. According to the expression of Bcl-2 and CD38 on tumor cells, 9 patients (56%) received Daratumumab (anti-CD38 monoclonal antibody) on day -6, 15 patients (94%) received venetoclax at 300 mg/m2/day on days -7 to -2. TCRαβ+/CD19+ depletion of PBSC with CliniMACS technology was implemented in all cases. The median dose of CD34+ cells in transplant was 11 x106/kg (range 7-18), α/β T cells - 40x103/kg (range 11- 139). Modified (CD45RA-depleted) donor lymphocyte infusions (DLI) were administered to 15 pts, 9 pts received modified DLI on day 0. Result Primary engraftment was achieved in 13 (81%) of 16 pts. The median time to ANC and platelets recovery was 14 days (11-22). Engraftment was 100% (10 of 10) among patients with acute leukemia and 50% (3 of 6) among patients with JMML. Three patients with JMML had early disease progression. There were no significant toxic effects after HSCT and no cases of transplant-related mortality. The median NK- cells count by the day +30 was 0,185 x 106/ml (range 0,019- 0,472), the median levels of αβ T cells and gd T cells were 0,045 x 106 /ml (range 0 - 0,364) and 0,07 x 106 /ml (range 0 - 0,349, respectively. Acute GVHD grade 1-2 was developed in 2 pts (15%), none of them required systemic immunosuppressive therapy. There were no cases of chronic GVHD. One (7,6%) patient with AML relapsed on day +61. Three pts (1 with AML and 2 with JMML) died from disease progression, 1 patient with JMML died from complications after the second HSCT. At the moment of reporting 12 pts (9 of 10 with acute leukemia and 3 of 6 with JMML) are alive, in complete remission with a median follow up of 3 months (1,5-7m). Conclusion We suggest that addition of venetoclax and datatumumab to the backbone of myeloablative haploidentical HSCT with αβ T cell depletion is not associated with increased toxicity and may lead to improved early outcomes in a cohort of pediatric patients with chemorefractory acute leukemia. This approach can be further tested in a prospective trial with the goal to increase the anti-leukemic efficacy of HSCT. Disclosures No relevant conflicts of interest to declare.
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- 2018
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21. Transplantation from Matched Unrelated and Haploidentical Donor in Pediatric Severe Aplastic Anemia: Experience with TCR Alpha/Beta and CD19 Depletion As Graft Processing Method
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Elena Raykina, Michael Maschan, Galina Novichkova, Maria Ilyushina, Svetlana Kozlovskaya, Elena Kurnikova, Daria Shasheleva, Anna Bogoyavlenskaya, Elena Boyakova, Larisa Shelikhova, Alexey Kazachenok, Alexey Maschan, Zhanna Shekhovtsova, Varvara Briliantova, Pavel Trakhtman, and Dmitriy Balashov
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Fludarabine ,Transplantation ,Graft-versus-host disease ,Internal medicine ,medicine ,Alemtuzumab ,Cumulative incidence ,Aplastic anemia ,business ,medicine.drug - Abstract
Introduction Hematopoietic stem cell transplantation from non-sibling donors remains the only curative option for severe aplastic anemia patients refractory to ATG/CsA immunosuppression. Although the results of MUD and haploidentical transplantation in SAA have improved significantly, graft-versus host disease (GVHD) remains a serious problem, associated with significant morbidity and mortality. We investigated the role of new method of graft processing - TCR alpha/beta depletion as a way to improve the results of MUD and haploidentical transplants in SAA. Patients and methods Forty two patients with SAA were treated since November 2012 till February 2016. Median age at HSCT was 11(3-22) years, 27 male/15 female. All pts. were refractory/relapsed (36/6) after at least two courses of ATG/CsA, 3 pts. had concurrent severe hemolytic PNH. Time from diagnosis to transplant was 17(143-8,6)/15(99-5,5) months. Donors were unrelated volunteers in 32 cases, haploidentical parents in 10 cases. Preparative regimen included cyclophosphamide 100-150 mg/kg, fludarabine 150mg/kg, ATG and 2-6Gy thoraco-abdominal irradiation, in haplo transplants patients additionaly received thiophosphamide at 10mg/kg. Two patients recieved alemtuzumab instead of ATG because of anaphylaxis. Post-transplant GVHD prophylaxis included Tacro and Mtx on days +1, +3, +6. PBSC grafts were depleted of TCR alpha/beta cells and CD19 cells with CliniMACS device as recommended by the manufacturer. Patients received a median of 10(6,0-23) x106 CD34 per kg, 8(1-39) x104 TCR alpha/beta per kg. Results All patients engrafted with a median of 15 days for WBC and 13,5 days for platelets. In 4 patients after MUD transplantation secondary graft failure (rejection) developed, two of them were successfully retransplanted. Cumulative incidence of aGVHD 2-3 was 9% (95% CI: 3-27%) and 40%(95% CI: 18-85%) in MUD and haplo respectively, 90% patients with aGVHD had only skin involvement. No grade 4 aGVHD detected. Cumulative incidence of grade 3 aGVHD was 3%(95% CI: 0,5-21%) and 10%(95% CI: 2-64%) in MUD and haplo, respectively. Cumulative incidence of cGVHD was 12%(95% CI: 0,5-58%) and 30%(95% CI: 11-77%) in MUD and haplo respectively. A median follow up is 2 years. Seven patients died of viral infection - CMV (2 pts.), viral infection - CMV plus GVHD (2 pts.), microangiopathy (1 pt), 2 pts. died after second transplantation (1 - disseminated toxoplasmosis, 1 - ADV and CMV and GVHD). Event and GVHD-free survival is 73%(95% CI: 57-89%) and 60% (95% CI: 30-90%) in MUD and haplo respectively (pic.1) Overall survival is 86%(95% CI: 74-99%) and 78%(95% CI: 50-100%) respectively for MUD and haploidentical (pic.2). Prolonged stable mixed chimerism in T-cells was detected in recipients of MUD grafts in contrast to haploidentical grafts (pic/3). Conclusion TCR alpha/beta depletion is a robust platform for allogeneic transplantation from MUD and haploidentical donors in severe aplastic anemia. Results should be further improved by additional measures to control viral infections and prevent rejection in MUD transplants. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
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- 2016
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22. Information literacy of older people: Social aspects of the problem
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Akhtyan, A. G., Anikeeva, O. A., Sizikova, V. V., Shimanovskaya, Y. V., Starovoytova, L. I., Medvedeva, G. P., and Svetlana Kozlovskaya
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