Elena Gutovskaya - Academia.edu (original) (raw)

Papers by Elena Gutovskaya

Research paper thumbnail of Low doses of decitabine for prevention of relapse after allogeneic hematopoietic stem cell transplantation: a single-center experience

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2018

59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-г... more 59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-гематолог, отделение трансплантации гемопоэтических стволовых клеток № 1 НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России.

Research paper thumbnail of The use of plerixafor and g-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2017

Research paper thumbnail of TCRαβ+ and CD19+ depletion in unrelated and haploidentical hematopoietic stem cell transplantation in children with primary immunodeficiencies

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2016

Research paper thumbnail of Treosulfan-Based Conditioning Before TCR ÅSS/CD19 - Depleted Stem Cell Transplantation for Patients with Primary Hemophagocytic Lymphohistiocytosis

Research paper thumbnail of 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

Blood, Nov 29, 2018

Introduction Relapse, graft-versus-host disease (GvHD) and associated non-relapse mortality are t... more 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…

Research paper thumbnail of Posttransplant lymphoproliferative disorder in children after allogeneic hematopoietic stem cell transplantation: a single-center experience and literature review

Cellular therapy and transplantation, Jul 31, 2017

Research paper thumbnail of Comparative analysis of late effects after treosulfan- and busulfan-based myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in children

Research paper thumbnail of Treosulfan-Based Conditioning Before TCR ÅSS/CD19 - Depleted Stem Cell Transplantation for Patients with Primary Hemophagocytic Lymphohistiocytosis

Research paper thumbnail of The use of plerixafor and g-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2017

Research paper thumbnail of 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

Blood, 2018

Introduction Relapse, graft-versus-host disease (GvHD) and associated non-relapse mortality are t... more 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 13...

Research paper thumbnail of Tcrαβ+/CD19+-Depletion in Hematopoietic Stem Cells Transplantation from Matched Unrelated and Haploidentical Donors Following Treosulfan or TBI-Based Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients

Blood, 2016

Introduction Relapse, graft-versus-host disease (GvHD) and GvHD-associated mortality are major ob... more Introduction Relapse, graft-versus-host disease (GvHD) and GvHD-associated mortality are major obstacles to success of transplantation from unrelated and haploidentical donors in children with acute lymphoblastic leukemia. Future directions will focus on optimizing conditioning regimens and enhancing graft-versus-leukemia effect. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes, which permits to maintain mature donor-derived natural killer cells and γδ(+) T cells in the graft may improve GvHD control, immune reconstitution and prevent the relapse. Patients and methods : A total of 67 pediatric patients with acute lymphoblastic leukemia (T-ALL- 26, B-ALL-41, 29 female, 38 male, median age 9,4 years, range 0,15-20) underwent allogeneic HSCT between May 2012 and May 2016. Forty two patients received haploidentical graft, 25 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 19pts., CR2 in 35 pts. and CR>2 13 pts. Transplantation in CR1 was pe...

Research paper thumbnail of Mismatched related vs matched unrelated donors in TCRαβ/CD19-depleted HSCT for primary immunodeficiencies

Blood, 2019

Laberko et al report excellent survival outcomes for patients receiving TCRαβ/CD19-depleted hemat... more Laberko et al report excellent survival outcomes for patients receiving TCRαβ/CD19-depleted hematopoietic stem cell transplantation (HSCT) for primary immunodeficiencies, demonstrating comparable results with mismatched related and matched unrelated donors.

Research paper thumbnail of Low doses of decitabine for prevention of relapse after allogeneic hematopoietic stem cell transplantation: a single-center experience

Pediatric Hematology/Oncology and Immunopathology, 2018

59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-г... more 59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-гематолог, отделение трансплантации гемопоэтических стволовых клеток № 1 НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России.

Research paper thumbnail of Evaluation of abatacept for GVHD prophylaxis in patients with non-malignant diseases after hematopoietic stem cell transplantation

Pediatric Hematology/Oncology and Immunopathology, 2019

Graft-versus-host diseases (GVHD) is one of most significant complication after allogeneic hemato... more 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...

Research paper thumbnail of 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

Biology of Blood and Marrow Transplantation, 2018

Our initial experience with hematopoietic stem cell transplantation (HSCT) from a matched unrelat... more 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.

Research paper thumbnail of BK virus nephropathy in a pediatric patient after hematopoietic stem cell transplantation

Pediatric transplantation, 2015

We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration ... more We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration of renal function 13 months after HSCT for myelodysplastic syndrome. BK virus nephropathy was suspected and confirmed. After reduction of immunosuppression and treatment with IVIG, leflunomide, ciprofloxacin, and cidofovir, clearance of BK virus from blood was achieved, and further progression or renal failure was prevented. We believe that BK virus nephropathy should be considered in cases of renal function deterioration in all immunocompromised patients.

Research paper thumbnail of TCRαβ+ and CD19+ depletion in unrelated and haploidentical hematopoietic stem cell transplantation in children with primary immunodeficiencies

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2016

Research paper thumbnail of Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome

Journal of Clinical Immunology

Research paper thumbnail of TCR Alpha/Beta and CD19 Depletion in Transplantation from Matched Unrelated and Haploidentical Donors in Pediatric Leukemia Patients: Comparison of Two Gvhd Prophylaxis Regimens

Biology of Blood and Marrow Transplantation, 2016

receiving bulk HPC infusion. In addition, CD4+ cell count on day 180, TRM and relapse rates were ... more receiving bulk HPC infusion. In addition, CD4+ cell count on day 180, TRM and relapse rates were similar between the two groups. We also observed that with current mobilization techniques it was unlikely that more than 60% of normal donors would be able to collect more than 7x10E6 CD34+ cells/kg recipient weight for adult recipients.

Research paper thumbnail of Low doses of decitabine for prevention of relapse after allogeneic hematopoietic stem cell transplantation: a single-center experience

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2018

59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-г... more 59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-гематолог, отделение трансплантации гемопоэтических стволовых клеток № 1 НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России.

Research paper thumbnail of The use of plerixafor and g-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2017

Research paper thumbnail of TCRαβ+ and CD19+ depletion in unrelated and haploidentical hematopoietic stem cell transplantation in children with primary immunodeficiencies

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2016

Research paper thumbnail of Treosulfan-Based Conditioning Before TCR ÅSS/CD19 - Depleted Stem Cell Transplantation for Patients with Primary Hemophagocytic Lymphohistiocytosis

Research paper thumbnail of 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

Blood, Nov 29, 2018

Introduction Relapse, graft-versus-host disease (GvHD) and associated non-relapse mortality are t... more 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…

Research paper thumbnail of Posttransplant lymphoproliferative disorder in children after allogeneic hematopoietic stem cell transplantation: a single-center experience and literature review

Cellular therapy and transplantation, Jul 31, 2017

Research paper thumbnail of Comparative analysis of late effects after treosulfan- and busulfan-based myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in children

Research paper thumbnail of Treosulfan-Based Conditioning Before TCR ÅSS/CD19 - Depleted Stem Cell Transplantation for Patients with Primary Hemophagocytic Lymphohistiocytosis

Research paper thumbnail of The use of plerixafor and g-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2017

Research paper thumbnail of 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

Blood, 2018

Introduction Relapse, graft-versus-host disease (GvHD) and associated non-relapse mortality are t... more 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 13...

Research paper thumbnail of Tcrαβ+/CD19+-Depletion in Hematopoietic Stem Cells Transplantation from Matched Unrelated and Haploidentical Donors Following Treosulfan or TBI-Based Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients

Blood, 2016

Introduction Relapse, graft-versus-host disease (GvHD) and GvHD-associated mortality are major ob... more Introduction Relapse, graft-versus-host disease (GvHD) and GvHD-associated mortality are major obstacles to success of transplantation from unrelated and haploidentical donors in children with acute lymphoblastic leukemia. Future directions will focus on optimizing conditioning regimens and enhancing graft-versus-leukemia effect. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes, which permits to maintain mature donor-derived natural killer cells and γδ(+) T cells in the graft may improve GvHD control, immune reconstitution and prevent the relapse. Patients and methods : A total of 67 pediatric patients with acute lymphoblastic leukemia (T-ALL- 26, B-ALL-41, 29 female, 38 male, median age 9,4 years, range 0,15-20) underwent allogeneic HSCT between May 2012 and May 2016. Forty two patients received haploidentical graft, 25 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 19pts., CR2 in 35 pts. and CR>2 13 pts. Transplantation in CR1 was pe...

Research paper thumbnail of Mismatched related vs matched unrelated donors in TCRαβ/CD19-depleted HSCT for primary immunodeficiencies

Blood, 2019

Laberko et al report excellent survival outcomes for patients receiving TCRαβ/CD19-depleted hemat... more Laberko et al report excellent survival outcomes for patients receiving TCRαβ/CD19-depleted hematopoietic stem cell transplantation (HSCT) for primary immunodeficiencies, demonstrating comparable results with mismatched related and matched unrelated donors.

Research paper thumbnail of Low doses of decitabine for prevention of relapse after allogeneic hematopoietic stem cell transplantation: a single-center experience

Pediatric Hematology/Oncology and Immunopathology, 2018

59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-г... more 59 о Р и г и н А л ь н ы е с т А т ь и Контактная информация: Илюшина Мария Александровна, врач-гематолог, отделение трансплантации гемопоэтических стволовых клеток № 1 НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России.

Research paper thumbnail of Evaluation of abatacept for GVHD prophylaxis in patients with non-malignant diseases after hematopoietic stem cell transplantation

Pediatric Hematology/Oncology and Immunopathology, 2019

Graft-versus-host diseases (GVHD) is one of most significant complication after allogeneic hemato... more 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...

Research paper thumbnail of 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

Biology of Blood and Marrow Transplantation, 2018

Our initial experience with hematopoietic stem cell transplantation (HSCT) from a matched unrelat... more 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.

Research paper thumbnail of BK virus nephropathy in a pediatric patient after hematopoietic stem cell transplantation

Pediatric transplantation, 2015

We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration ... more We report the case of a seven-yr-old Caucasian girl who presented with progressive deterioration of renal function 13 months after HSCT for myelodysplastic syndrome. BK virus nephropathy was suspected and confirmed. After reduction of immunosuppression and treatment with IVIG, leflunomide, ciprofloxacin, and cidofovir, clearance of BK virus from blood was achieved, and further progression or renal failure was prevented. We believe that BK virus nephropathy should be considered in cases of renal function deterioration in all immunocompromised patients.

Research paper thumbnail of TCRαβ+ and CD19+ depletion in unrelated and haploidentical hematopoietic stem cell transplantation in children with primary immunodeficiencies

Voprosy gematologii/onkologii i immunopatologii v pediatrii, 2016

Research paper thumbnail of Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome

Journal of Clinical Immunology

Research paper thumbnail of TCR Alpha/Beta and CD19 Depletion in Transplantation from Matched Unrelated and Haploidentical Donors in Pediatric Leukemia Patients: Comparison of Two Gvhd Prophylaxis Regimens

Biology of Blood and Marrow Transplantation, 2016

receiving bulk HPC infusion. In addition, CD4+ cell count on day 180, TRM and relapse rates were ... more receiving bulk HPC infusion. In addition, CD4+ cell count on day 180, TRM and relapse rates were similar between the two groups. We also observed that with current mobilization techniques it was unlikely that more than 60% of normal donors would be able to collect more than 7x10E6 CD34+ cells/kg recipient weight for adult recipients.