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  Prognostic relevance of TLX3 (HOX11L2) expression in childhood T-cell acute lymphoblastic leukaemia treated with Berlin–Frankfurt–Münster (BFM) protocols containing early and late re-intensification elements

Attarbaschi, A., Pisecker, M., Inthal, A., Mann, G., Janousek, D., Dworzak, M., et al. (2010). Prognostic relevance of TLX3 (HOX11L2) expression in childhood T-cell acute lymphoblastic leukaemia treated with Berlin–Frankfurt–Münster (BFM) protocols containing early and late re-intensification elements. British Journal of Hematology, 148(2), 293-300. doi:10.1111/j.1365-2141.2009.07944.x.

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 Creators:
Attarbaschi, Andishe, Author
Pisecker, Markus, Author
Inthal, Andrea, Author
Mann, Georg, Author
Janousek, Dasa, Author
Dworzak, Michael, Author
Pötschger, Ulrike, Author
Ullmann, Reinhard1, Author           
Schrappe, Martin, Author
Gadner, Helmut, Author
Haas, Oskar A., Author
Panzer-Grümayer, Renate, Author
Strehl, Sabine, Author
Affiliations:
1Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479645              

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Free keywords: T-cell acute lymphoblastic leukaemia; TLX3; Prognosis
 Abstract: TLX3 expression (TLX3+) in childhood T-cell acute lymphoblastic leukaemia (T-ALL) seems to be associated with a poor prognosis when treated with regimens that lack early and/or late re-intensification therapy elements. Because such elements are essential components of the ALL-BFM (Berlin–Frankfurt–Münster) protocols, we evaluated whether TLX3+ T-ALL patients benefit from this type of therapy. Thirty-one/131 childhood T-ALL cases (24%) enrolled into four population-based Austrian ALL-BFM therapy studies were TLX3+. The male to female ratio was 3·5:1 and median age and leucocyte count at diagnosis were 8·7 years and 58·9 × 109/l, respectively. Twenty-four patients (77%) were good responders to prednisone. All were in complete remission after induction therapy. After a median observation time of 4·9 years (range 0·4–16·1 years) 28/31 TLX3+ cases remained in first complete remission after chemotherapy with one after additional stem cell transplantation. Although molecular disease was frequently present after a 4-drug induction therapy, final treatment outcome was excellent indicating that TLX3+ T-ALL cases may benefit from a BFM-type of ALL therapy with early and late re-intensification elements. Moreover, the fact that 2/3 relapses were also NUP214-ABL1+ suggests that these cases might represent the particular risk-prone TLX3+ subgroup that could benefit from a targeted tyrosine kinase inhibitor therapy.

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Language(s): eng - English
 Dates: 2010-01
 Publication Status: Issued
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Title: British Journal of Hematology
Source Genre: Journal
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Pages: - Volume / Issue: 148 (2) Sequence Number: - Start / End Page: 293 - 300 Identifier: ISSN: 0007-1048