1. ¹Department of Hematology/Hematological Biology, Cliniques Universitaires UCL Saint-Luc, Brussels, Belgium
2. ²Department of Hematology, Cliniques Universitaires ULB Erasme, Brussels, Belgium
3. ³Department of Epidemiology and Biostatistics, Université Catholique de Louvain, Brussels, Belgium
4. ⁴Center for Human Genetics, KU Leuven, Leuven, Belgium
5. ⁵Department of Hematology, UZ Leuven, Leuven, Belgium
6. ⁶Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
7. ⁷Department of Hematology, Cliniques Universitaires UCL de Mont-Godinne, Yvoir, Belgium

Correspondence: Professor E Van Den Neste, Department of Hematology, Cliniques Universitaires UCL Saint-Luc, 10 av. Hippocrate, 1200 Brussels, Belgium. E-mail: vandenneste@sang.ucl.ac.be

⁸These authors contributed equally to this work.

Received 4 December 2006; Revised 19 April 2007; Accepted 25 April 2007; Published online 31 May 2007.

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 IgV_H mutational status. Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgV_H 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. IgV_H 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. IgV_H 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.