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Alert Number 2

Deletion of 6q21 and Prognostic Risk

Date: March 19, 2004

Recent articles on our website have focused on the importance of FISH testing. Modern "best practices" call for risk stratification of CLL patients in order to make better therapy choices. So far, we have focused on four frequent chromosomal abnormalities, the 13q deletion (low risk), 12 Trisomy (Intermediate risk) and 11q deletion, 17p deletion (High risk). Below is an abstract that describes another abnormality, deletion of 6q. Based on what we know thus far, 6q deletion falls into the intermediate risk category, or "Bucket B". Those of you who are getting FISH testing in the near future may want to save this information, as well as ask your lab testing company whether they test for 6q deletion. Otherwise, this group of patients also gets lumped into the so-called "normal" FISH category.

For more information on CLL risk classification and FISH results, please read FISHing for Answers.

Be well,



Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis

A Cuneo, G M Rigolin, R Bigoni, C De Angeli, A Veronese, F Cavazzini, A Bardi, M G Roberti, E Tammiso, P Agostini, M Ciccone, M Della Porta, A Tieghi, L Cavazzini, M Negrini and G Castoldi

Institute of Hematology, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk' (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p-). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6 cases. IGVH mutational status revealed >98% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38+ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6q- group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6q- anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q- chromosome maintained its prognostic significance at multivariate analysis (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

Leukemia (2004) 18, 476-483. doi:10.1038/sj.leu.2403242

Published online 18 December 2003

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