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Chronic Lymphocytic Leukemia

Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine

Leukemia volume 21, pages 1715–1722 (2007)Cite this article

Abstract

Chromosomal translocations represent an important prognostic indicator in B-cell chronic lymphocytic leukemia (B-CLL). However, their value had been neither determined in homogeneously treated patients nor compared to that of IgVH mutational status. Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgVH and of TP53 mutational status before treatment with 2-chloro-2′-deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of the patients, including both balanced (n=12) and unbalanced (n=33) types. IgVH was mutated in 43% of the patients. Patients with translocations were more heavily pretreated (P=0.05), presented with more complex karyotypes (P<0.001), 17p abnormalities and TP53 mutations, and had a higher failure rate (59 vs 21% in patients without translocations, P=0.004). Patients with unbalanced translocations displayed a shorter median treatment-free survival (TFS, 6.9 vs 35.9 months, log rank 22.72, P<0.001) and overall survival (OS, 13.0 vs 68.0 months, log rank 16.51, P<0.001), as compared to patients without translocation. In multivariate analysis, unbalanced translocations were independently associated with therapeutic failure, short TFS and short OS. IgVH mutational status was independently associated with risk of failure and TFS, but not OS. In B-CLL patients treated with CdA, translocations are strong predictors of outcome.

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Acknowledgements

This text presents research results of the Belgian program of Interuniversity Poles of attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The study was supported by the Fund for Scientific Research of Flanders (FWO – Vlaanderen) grant no. G.0338.01 and by the Salus Sanguinis Foundation. VR was a recipient of a Télévie grant. We thank Betty Emanuel, Monique Rubens, Wim De Kelver and Frederik Claessens for expert technical assistance.

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  1. E Van Den Neste and V Robin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology/Hematological Biology, Cliniques Universitaires UCL Saint-Luc, Brussels, Belgium

    E Van Den Neste, V Robin, V Deneys, S Costantini, A Ferrant & L Michaux

  2. Department of Hematology, Cliniques Universitaires ULB Erasme, Brussels, Belgium

    V Robin

  3. Department of Epidemiology and Biostatistics, Université Catholique de Louvain, Brussels, Belgium

    J Francart & A Robert

  4. Center for Human Genetics, KU Leuven, Leuven, Belgium

    A Hagemeijer, M Stul, P Vandenberghe & L Michaux

  5. Department of Hematology, UZ Leuven, Leuven, Belgium

    P Vandenberghe

  6. Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium

    A Delannoy

  7. Department of Hematology, Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium

    A Sonet

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Correspondence to E Van Den Neste.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Van Den Neste, E., Robin, V., Francart, J. et al. Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine. Leukemia 21, 1715–1722 (2007). https://doi.org/10.1038/sj.leu.2404764

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