Publications by authors named "Julia Starichkova"

3 Publications

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T-cell tracking, safety, and effect of low-dose donor memory T-cell infusions after αβ T cell-depleted hematopoietic stem cell transplantation.

Bone Marrow Transplant 2021 Apr 17;56(4):900-908. Epub 2020 Nov 17.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 10 to 100 × 10/kg (haplo) and from 100 × 10 to 300 × 10 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.
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http://dx.doi.org/10.1038/s41409-020-01128-2DOI Listing
April 2021

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

Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial.

Bone Marrow Transplant 2018 03 21;53(3):264-273. Epub 2017 Dec 21.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant (n = 36) and non-malignant conditions (n = 17) received TCR alpha/beta depleted grafts from haploidentical (n = 25) or MUD (n = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 10/kg CD3 cells from haploidentical or 100 × 10/kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 10/kg in haploidentical transplants and 300 × 10/kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline (n = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.
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http://dx.doi.org/10.1038/s41409-017-0035-yDOI Listing
March 2018