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Laberko A, Idarmacheva A, Glushkova S, et al. Post-Transplantation Immunosuppression After TCRΑβ/CD19 Graft Depletion Does Not Improve HSCT Outcomes in Primary Immunodeficiency. Transplant Cell Ther. 2021;doi: 10.1016/j.jtct.2021.11.022.
Laberko, A., Idarmacheva, A., Glushkova, S., Pershin, D., Shelikhova, L., Maschan, M., Maschan, A., & Balashov, D. (2021). Post-Transplantation Immunosuppression After TCRΑβ/CD19 Graft Depletion Does Not Improve HSCT Outcomes in Primary Immunodeficiency. Transplantation and cellular therapy, . https://doi.org/10.1016/j.jtct.2021.11.022
Laberko, Alexandra, et al. "Post-Transplantation Immunosuppression After TCRΑβ/CD19 Graft Depletion Does Not Improve HSCT Outcomes in Primary Immunodeficiency." Transplantation and cellular therapy vol. (2021). doi: https://doi.org/10.1016/j.jtct.2021.11.022
Laberko A, Idarmacheva A, Glushkova S, Pershin D, Shelikhova L, Maschan M, Maschan A, Balashov D. Post-Transplantation Immunosuppression After TCRΑβ/CD19 Graft Depletion Does Not Improve HSCT Outcomes in Primary Immunodeficiency. Transplant Cell Ther. 2021 Dec 04; doi: 10.1016/j.jtct.2021.11.022. Epub 2021 Dec 04. PMID: 34875404.
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Transplant Cell Ther. 2021 Dec 04; doi: 10.1016/j.jtct.2021.11.022. Epub 2021 Dec 04.

Post-Transplantation Immunosuppression After TCRΑβ/CD19 Graft Depletion Does Not Improve HSCT Outcomes in Primary Immunodeficiency.

Transplantation and cellular therapy

Alexandra Laberko, Aishat Idarmacheva, Svetlana Glushkova, Dmitry Pershin, Larisa Shelikhova, Michael Maschan, Alexei Maschan, Dmitry Balashov

Affiliations

  1. Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Translational and Clinical Research Institute, Newcastle University; Newcastle-upon-Tyne, United Kingdom. Electronic address: [email protected].
  2. Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
  3. Laboratory of Hematopoietic Stem Cell Transplantation and Immunotherapy, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

PMID: 34875404 DOI: 10.1016/j.jtct.2021.11.022

Abstract

We recently demonstrated that TCRαβ+/CD19+ graft depletion successfully prevents severe acute and chronic graft-versus-host disease (GVHD) in pediatric patients with primary immunodeficiencies (PID) receiving transplants from both matched unrelated and mismatched related donors. However, in all patients, short-term post-hematopoietic stem cell transplantation (HSCT) immunosuppressive therapy (IST) was used. There are limited data on TCRαβ+/CD19+ graft depletion with no post-HSCT IST implementation. In the current study 74 PID patients who underwent first HSCT from matched unrelated (n=51) or mismatched related donors (n=23) with TCRαβ+/CD19+ graft depletion were included. All received as a conditioning regimen a combination of treosulfan with fludarabine and either melphalan or thiotepa. In all, thymoglobulin 5 mg/kg (days -5, -4, -3) and rituximab at day -1 were used. In 48 patients, various approaches to short-term post-transplantation IST were used, and 26 patients received no post-HSCT IST. The rates of engraftment, acute and chronic GVHD, survival, and mortality were similar in those who received and did not receive IST, with a slightly higher incidence of graft rejection in patients not receiving IST: 19% in the non-IST group against 13% in the IST group (P = .41). The incidence of cytomegalovirus reactivation was 50% and 39% (P = .50) and Epstein-Barr virus reactivation 10% and 0 (P = .20) in the IST and non-IST groups, respectively. No grade 4 adverse events were seen in both groups, although in 19 of 40 (47.5%) patients receiving calcineurin inhibitors, the therapy was discontinued before day 45. More robust immune recovery with both T- and B-lymphocytes was observed in the non-IST group. To conclude, TCRαβ+/CD19+ in combination with particular serotherapy effectively prevents severe acute and chronic GVHD in PID. Regarding remaining risks of infectious complications and additional drug-related toxicity, there are no benefits to post-HSCT IST use in these patients.

Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Keywords: Graft-versus-host disease prophylaxis; Hematopoietic stem cell transplantation; Post-transplant immunosuppression; Primary immunodeficiency; TCRαβ/cd19 depletion

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