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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

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons38805

Dornmair,  Klaus
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Citation

Schuster, F. R., Hubner, B., Fuehrer, M., Eckermann, O., Gombert, M., Dornmair, K., et al. (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. BLOOD CANCER JOURNAL, 1: e8. doi:10.1038/bcj.2011.6.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-3D49-C
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. Blood Cancer Journal (2011) 1, e8; doi:10.1038/bcj.2011.6; published online 4 March 2011