Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia.
| Title: | Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia. |
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| Authors: | Glushkova S; Dmitry Rogachev National Medical Research Center of Laboratory of Transplantation Immunology and Immunotherapy, Moscow, Russia. Electronic address: rizoiu.svetlana@gmail.com.; Shelikhova L; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Voronin K; Dmitry Rogachev National Medical Research Center of Department of Statistics, Moscow, Russia.; Dunaikina M; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Blagov S; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Pershin D; Dmitry Rogachev National Medical Research Center of Laboratory of Transplantation Immunology and Immunotherapy, Moscow, Russia.; Vedmedskaya V; Dmitry Rogachev National Medical Research Center of Laboratory of Transplantation Immunology and Immunotherapy, Moscow, Russia.; Fadeeva M; Dmitry Rogachev National Medical Research Center of Laboratory of Transplantation Immunology and Immunotherapy, Moscow, Russia.; Arakelyan S; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Muzalevskii Y; Dmitry Rogachev National Medical Research Center of Department of Transfusion Medicine, Moscow, Russia.; Kazachenok A; Dmitry Rogachev National Medical Research Center of Department of Transfusion Medicine, Moscow, Russia.; Skvortsova Y; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Balashov D; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Maschan A; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia.; Maschan M; Dmitry Rogachev National Medical Research Center of Department of Hematopoietic Stem Cell Transplantation, Moscow, Russia. |
| Source: | Cytotherapy [Cytotherapy] 2025 Nov; Vol. 27 (11), pp. 1344-1350. Date of Electronic Publication: 2025 Aug 05. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2013- : London : Elsevier; Original Publication: Oxford, England : ISIS Medical Media, c1999- |
| MeSH Terms: | Hematopoietic Stem Cell Transplantation*/methods ; Receptors, Antigen, T-Cell, alpha-beta*/immunology ; Receptors, Antigen, T-Cell, alpha-beta*/metabolism ; Lymphocyte Depletion*/methods ; T-Lymphocytes*/immunology ; Leukemia*/therapy ; Leukemia*/immunology ; Leukemia*/mortality; Killer Cells, Natural/immunology ; Humans ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Retrospective Studies ; Treatment Outcome ; Infant ; Transplantation, Haploidentical |
| Abstract: | Background: Functional immune reconstitution (IR) is a key factor in determining the success of hematopoietic stem cell transplantation (HSCT). IR depends on a number of factors and is typically delayed by ex vivo T cell depletion of the graft. αβ T cell depletion (αβ TCD) platform was reported to be associated with improved IR.; Objective: In this retrospective study, we've focused on a homogeneous cohort of 262 children with acute leukemia first transplanted in complete remission, and investigate whether very early recovery of NK and T cells, as well as αβ and γδ T subsets, is associated with clinical outcomes.; Study Design: The grafts were obtained from apheresis products and processed by αβ TCD method. IR of lymphocyte subpopulations was measured in peripheral blood (PB) on day +30 after HSCT by flow cytometry.; Results: The study suggests that in the early post-HSCT period, higher absolute number of T cells, despite being far below the normal range and having a rather limited T cell receptors repertoire, is associated with radically improved non-relapse mortality (NRM). Multivariate analysis confirmed the independent effect of T-cell IR on NRM. Our results show that each 10-fold increase in T cell PB count is associated with a 2.1-fold reduction in NRM (cause-specific Hazard Ratio (csHR) 0.47), independent from other important factors such as aGVHD or serotherapy use.; Conclusion: Based on these results we suggest that T cells recovery on day +30 after HSCT can be used in predicting NRM risk in the setting of αβ TCD HSCT. Early intervention for IR improvement can be planned.; (Copyright © 2025 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest M.M. received lecturer’s fee from Miltenyi Biotec; all other authors declare no conflict of interest in relation to the current manuscript. |
| Contributed Indexing: | Keywords: ATG; HSCT outcomes; T cells; haploidentical HSCT; immune reconstitution; leukemia; non-relapse mortality; pediatric patients; αβ T cell depletion |
| Substance Nomenclature: | 0 (Receptors, Antigen, T-Cell, alpha-beta) |
| Entry Date(s): | Date Created: 20250903 Date Completed: 20251025 Latest Revision: 20251025 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.jcyt.2025.07.005 |
| PMID: | 40900069 |
| Database: | MEDLINE |
Journal Article