Svetlana Glushkova, Larisa Shelikhova, Kirill Voronin, Maria Dunaikina, Sergey Blagov, Dmitriy Pershin, Viktoria Vedmedskaya, Maria Fadeeva, Susanna Arakelyan, Yakov Muzalevskii, Alexei Kazachenok, Yuliya Skvortsova, Dmitry Balashov, Alexei Maschan, Michael Maschan
{"title":"在α / β T细胞缺失的单倍同型造血干细胞移植后,T细胞的早期恢复预示着白血病儿童的预后。","authors":"Svetlana Glushkova, Larisa Shelikhova, Kirill Voronin, Maria Dunaikina, Sergey Blagov, Dmitriy Pershin, Viktoria Vedmedskaya, Maria Fadeeva, Susanna Arakelyan, Yakov Muzalevskii, Alexei Kazachenok, Yuliya Skvortsova, Dmitry Balashov, Alexei Maschan, Michael Maschan","doi":"10.1016/j.jcyt.2025.07.005","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia.\",\"authors\":\"Svetlana Glushkova, Larisa Shelikhova, Kirill Voronin, Maria Dunaikina, Sergey Blagov, Dmitriy Pershin, Viktoria Vedmedskaya, Maria Fadeeva, Susanna Arakelyan, Yakov Muzalevskii, Alexei Kazachenok, Yuliya Skvortsova, Dmitry Balashov, Alexei Maschan, Michael Maschan\",\"doi\":\"10.1016/j.jcyt.2025.07.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":50597,\"journal\":{\"name\":\"Cytotherapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jcyt.2025.07.005\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jcyt.2025.07.005","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia.
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.
期刊介绍:
The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.