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Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia

Journal Article:

Abstract

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.
Authors:
Schuster, F R; Hubner, B; [1]  Führer, M; [2]  Eckermann, O; Gombert, M; [1]  Dornmair, K; [3]  Binder, V; Reuther, S; Krell, P; [1]  Keller, T; [4]  Borkhardt, A [1] 
  1. Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany)
  2. Department of Pediatric Oncology and Hematology, Dr von Haunersches Children's Hospital, University of Munich, Munich (Germany)
  3. Department for Clinical Neuroimmunology, University of Munich, Munich (Germany)
  4. Acomed, statistical analysis GmbH, Leipzig (Germany)
Publication Date:
Mar 01, 2011
Product Type:
Journal Article
Resource Relation:
Journal Name: Blood Cancer Journal; Journal Volume: 1; Journal Issue: 3; Other Information: PMCID: PMC3255274; PMID: 22829127; OAI: oai:pubmedcentral.nih.gov:3255274; Copyright (c) 2011 Macmillan Publishers Limited; This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/; Country of input: International Atomic Energy Agency (IAEA)
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANEMIAS; BONE MARROW; CHILDREN; PATIENTS; RECEPTORS; REDUCTION; STEM CELLS; THERAPY
OSTI ID:
22343074
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 2044-5385; Other: PII: bcj20116; TRN: GB15$0109049408
Availability:
Available from http://dx.doi.org/10.1038/bcj.2011.6; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255274
Submitting Site:
INIS
Size:
page(s) 8
Announcement Date:
Jun 19, 2015

Journal Article:

Citation Formats

Schuster, F R, Hubner, B, Führer, M, Eckermann, O, Gombert, M, Dornmair, K, Binder, V, Reuther, S, Krell, P, Keller, T, and Borkhardt, A. Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. United Kingdom: N. p., 2011. Web. doi:10.1038/BCJ.2011.6.
Schuster, F R, Hubner, B, Führer, M, Eckermann, O, Gombert, M, Dornmair, K, Binder, V, Reuther, S, Krell, P, Keller, T, & Borkhardt, A. Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia. United Kingdom. doi:10.1038/BCJ.2011.6.
Schuster, F R, Hubner, B, Führer, M, Eckermann, O, Gombert, M, Dornmair, K, Binder, V, Reuther, S, Krell, P, Keller, T, and Borkhardt, A. 2011. "Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia." United Kingdom. doi:10.1038/BCJ.2011.6. https://www.osti.gov/servlets/purl/10.1038/BCJ.2011.6.
@misc{etde_22343074,
title = {Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia}
author = {Schuster, F R, Hubner, B, Führer, M, Eckermann, O, Gombert, M, Dornmair, K, Binder, V, Reuther, S, Krell, P, Keller, T, and Borkhardt, A}
abstractNote = {One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.}
doi = {10.1038/BCJ.2011.6}
journal = {Blood Cancer Journal}
issue = {3}
volume = {1}
journal type = {AC}
place = {United Kingdom}
year = {2011}
month = {Mar}
}