Evidence map›Paper›PMID 39923938›Full record

ArticleTransplantation and cellular therapy2025

Relevance of Recent Thymic Emigrants Following Allogeneic Hematopoietic Cell Transplantation for Pediatric Patients with Inborn Errors of Immunity.

Daniel Drozdov, Xianghua Luo, Rebecca A Marsh, Roshini S Abraham, Christen L Ebens

Abstract read
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Article in Transplantation and cellular therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Daniel DrozdovDivision of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Hematology/Oncology, Children's Hospital, Kantonsspital Aarau, Aarau, Switzerland; Division of Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland. Electronic address: daniel.drozdov@bluewin.ch.
Xianghua LuoBiostatistics Core at Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
Rebecca A MarshDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio; Pharming Healthcare, Warren, New Jersey.
Roshini S AbrahamDepartment of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Christen L EbensDivision of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Bruce R Blazar · 1995 to 2026
$48.2M
NCI NIH HHS P01 CA065493
6 · The paper itself

Abstract

backgroundAllogeneic hematopoietic cell transplantation (HCT) can be curative for many inborn errors of immunity (IEI). Timely neothymopoiesis is paramount to favorable clinical outcomes after HCT. Neothymopoiesis can be quantified by flow cytometric measurement of circulating recent thymic emigrants (RTE; CD31+CD4+CD45RA+ T cells).

objectivesWe hypothesized that decreased RTE would be associated with baseline HCT characteristics of older age at time of HCT and exposure to greater HCT conditioning intensity, as well as with HCT outcomes including mixed (<95%) lymphoid donor chimerism and presence of acute graft-versus-host disease (GvHD). STUDY

designIn this retrospective analysis two cohorts of pediatric IEI HCT recipients were identified at two centers that collected RTE data following allogeneic HCT. For both cohorts, patient and HCT information was recorded including but not limited to patient age, lymphoid donor chimerism, and occurrence of acute GvHD. Mixed effects models were fitted for the repeated measures of RTE with these covariates and time.

resultsBetween 2012 and 2021, a total of 162 pediatric IEI HCT recipients transplanted across both cohorts were eligible for inclusion. Cohort A (n = 34) included 23 males (68%). Median age at HCT was 2.2 years (interquartile range (IQR) 0.8 to 10.8). Eight (23.5%) underwent reduced intensity (RIC), 23 (67.7%) reduced toxicity myeloablative (RTC), and 3 (8.8%) myeloablative (MAC) conditioning. All received alemtuzumab serotherapy. Cohort B (n = 128) included 87 males (68%). Median age at HCT was 1.4 years (IQR 0.7 to 5.3). Seventy-six (59.4%) underwent RIC, 38 (29.7%) RTC, and 14 (10.9%) MAC. RIC and RTC patients received alemtuzumab serotherapy, MAC antithymocyte globulin. In the linear mixed effect model for RTE at 1 year after HCT for Cohort A, significant negative associations included increasing age (P < .0001) and RTC compared to RIC (P < .01). In the linear mixed effects model for RTE at 1 year after HCT for Cohort B, significant negative associations included increasing age (P < .0001), grade 2 to 4 acute GvHD (compared to grade 0 to 1; P < .01), MAC compared to RIC (P < .0001), MAC compared to RTC (P < .01), and RTC compared to RIC (P = .03).

conclusionsSerial measurement of RTE is a useful assessment of thymic function after HCT. In pediatric patients with IEI, older age at transplantation, greater intensity of conditioning, and occurrence of grade 2 to 4 acute GvHD were strongly associated with slower thymic-derived immune reconstitution. Mixed lymphoid donor chimerism was not associated with RTE in the linear mixed effects model. In addition to augmenting current anticipatory guidance on HCT outcomes, these findings may guide personalization of regimens to optimize clinical outcomes in IEI HCT.

Indexed as

Hematopoietic Stem Cell TransplantationThymus GlandAdolescentChildChild, PreschoolFemaleGraft vs Host DiseaseHumansInfantMaleRetrospective StudiesTransplantation ConditioningTransplantation, HomologousImmune reconstitutionNeothymopoiesisRecent thymic emigrantsReduced intensity conditioning

Identifiers

PMID39923938
PMCPMC11957927

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.