Publications by authors named "Svetlana Radygina"

3 Publications

  • Page 1 of 1

Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome.

J Clin Immunol 2020 08 30;40(6):861-871. Epub 2020 Jun 30.

Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela str, Moscow, Russia, 117997.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150 mg/m, cyclophosphamide 20-40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Twelve patients additionally received low-dose busulfan 4 mg/kg (Bu group) and 10 patients (including 2 recipients of a second HSCT) treosulfan (Treo group) 30 g/m. Overall and event-free survival were 0.75 vs 1 (p = 0.16) and 0.47 vs 0.89 (p = 0.1) in the Bu and Treo groups, respectively. In the Bu group, four patients developed graft rejection, and three died: two died of de novo and relapsed lymphomas and one died of adenoviral hepatitis. The four living patients exhibited split chimerism with predominantly recipient myeloid cells and predominantly donor T and B lymphocytes. In Treo group, one patient developed rhabdomyosarcoma. There was no difference in the incidence of GVHD, viral reactivation, or early toxicity between either group. Low-dose Bu-containing CR in NBS leads to increased graft failure and low donor myeloid chimerism. Treo-CR followed by TCRαβ/CD19-depleted HSCT demonstrates a low level of early transplant-associated toxicity and enhanced graft function with stable donor chimerism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-020-00811-9DOI Listing
August 2020

BCG-Related Inflammatory Syndromes in Severe Combined Immunodeficiency After TCRαβ+/CD19+ Depleted HSCT.

J Clin Immunol 2020 05 6;40(4):625-636. Epub 2020 May 6.

Department of Immunology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela str., Moscow, Russia, 117997.

Introduction: The live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID.

Patients And Methods: We reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαβ+/CD19+ graft depletion. All BCG-vaccinated patients received anti-mycobacterial therapy pre- and post-HSCT. Post-transplant immunosuppression consisted of tacrolimus in 10 patients and of 8 mg/kg tocilizumab (d-1, + 14, + 28) and 10 mg/kg abatacept (d-1, + 5, + 14, + 28) in 11 patients.

Results: Twelve patients, five of whom had BCG infection prior to HSCT, developed BCG-related inflammatory syndromes (BCG-IS). Five developed early BCG-IS with the median time of manifestation 11 days after HSCT, corresponding with a dramatic increase of CD3+TCRγδ+ in at least two patients. Early BCG-IS was noted in only one out of 11 patients who received tocilizumab/abatacept and 4 out of 11 patients who did not. Seven patients developed late BCG-IS which corresponded to T cell immune recovery; at the time of manifestation (median 4.2 months after HSCT), the median number of CD3+ cells was 0.42 × 10/ and CD3+CD4+ cells 0.27 × 10/l. In all patients, late BCG-IS was controlled with IL-1 or IL-6 inhibitors.

Conclusion: BCG-vaccinated SCID patients undergoing allogeneic HSCT with TCRαβ+/CD19+ graft depletion are at an increased risk of early and late BCG-IS. Anti-inflammatory therapy with IL-1 and IL-6 blockade is efficient in the prevention of early and treatment of late BCG-IS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-020-00774-xDOI Listing
May 2020

αβ T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation without Antithymocyte Globulin in Children with Chemorefractory Acute Myelogenous Leukemia.

Biol Blood Marrow Transplant 2019 05 21;25(5):e179-e182. Epub 2019 Jan 21.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia. Electronic address:

We evaluated the outcome of αβ T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (n = 10) or relapsed refractory (n = 12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by αβ T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that αβ T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.01.023DOI Listing
May 2019