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Blood, 15 January 2006, Vol. 107, No. 2, pp. 742-751.
Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-05-2093.
 Previous Article | Next Article 
Submitted May 24, 2005
Accepted September 7, 2005
Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia
Christine Mayr, Michael R Speicher, David M Kofler, Raymund Buhmann, John Strehl, Raymonde Busch, Michael Hallek, and Clemens-Martin Wendtner*
GSF-National Research Center for Environment and Health, Munich, Germany; Medical Clinic III, Klinikum rosshadern Medical Center, Ludwig-Maximillians-University of Munich, Munich, Germany; Institute of Human Genetics, Technical University of Munich, Munich, Germany
GSF-National Research Center for Environment and Health, Munich, Germany; Institute of Human Genetics, Technical University of Munich, Munich, Germany
GSF-National Research Center for Environment and Health, Munich, Germany; Medical Clinic III, Klinikum rosshadern Medical Center, Ludwig-Maximillians-University of Munich, Munich, Germany; Medical Clinic I, University of Cologne, Cologne, Germany
GSF-National Research Center for Environment and Health, Munich, Germany; Medical Clinic III, Klinikum rosshadern Medical Center, Ludwig-Maximillians-University of Munich, Munich, Germany
Medical Clinic, University of Bonn, Bonn, Germany
Institute of Medical Statistics and Epidemiology, Technical University of Munich, Munich, Germany
* Corresponding author; email: clemens.wendtner{at}uni-koeln.de.
In CLL chromosomes usually evade detailed cytogenetic analyses, as cells poorly respond to the traditionally used set of mitogens. We applied novel technologies, i.e. stimulation of CLL cells either with CD40 ligand or with a combination of CpG-oligodeoxynucleotides and IL-2, to increase the frequency of metaphase spreads for a detailed chromosome analysis in 96 CLL patients. This approach revealed that translocations occur in 33 of 96 (34%) of our patients with CLL. The presence of translocations defines a new prognostic subgroup as these patients have a highly significant shorter median treatment-free survival (24 mo vs. 106 mo; p<0.001) and a significantly inferior overall survival (median OS: 94 mo) compared to patients without translocations (346 mo; p<0.001). In a multivariate analysis, including Binet stage, presence of a complex karyotype, CD38 expression and 17p deletions, translocations proved to be the prognostic marker with the highest impact for an unfavorable clinical outcome (p<0.001). In summary, we identified a new subgroup of patients with CLL defined by chromosomal translocations and poor prognosis. Our data may facilitate the identification of molecular events crucial for transforming activity in this disease and should have implications for a risk-adapted clinical management of patients with CLL.
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