Clinical heterogeneity of de novo 11q deletion chronic lymphocytic leukaemia: prognostic relevance of extent of 11q deleted nuclei inside leukemic clone

Abstract

Deletion on the long arm of chromosome 11 occurs in 5-20% of chronic lymphocytic leukaemia (CLL) patients. We analysed clinical-biological characteristics of 131 CLL patients carrying 11q deletion documented before therapy (de novo 11q deleted CLL). De novo 11q deleted CLL were characterized by high frequencies of unmutated immunoglobulin variable heavy genes, multiple fluorescence in situ hybridization aberrations and lymph node involvement. Factors significantly associated with shorter time to first treatment (TTFT) were advanced Binet stages, high white blood cell count, increased β2 -microglobulin levels, 17p in addition, splenomegaly and more extensive lymphadenopathy. We found that patients with <25% 11q deleted nuclei (n = 22) experienced longer TTFT compared with patients with ≥25% 11q deleted nuclei (n = 87; median TTFT, 40 vs. 14 months, p = 0.011) and also showed better response to treatments (complete response, 50% vs. 21%, p = 0.016). The variables identified by multivariate analysis as independently associated with reduced TTFT were advanced Binet stages [hazard ratio (HR) 4.69; p < 0.001] and ≥25% 11q deleted nuclei (HR 4.73; p = 0.004). De novo 11q deleted CLLs exhibit variable clinical outcome. The percentage of deleted nuclei inside leukemic clone should be included in the prognostic definition of therapy-naïve 11q deleted CLL patients.

The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium experience

“…In contrast to 17p and 13q deletion groups, patients with 11q deletion did not exhibit a statistically significant association between TTFT and percentage of abnormal nuclei. Thus, we were unable to confirm an association between high percentage 11q deletion and adverse outcomes reported by Marasca et al (2013) and Jain et al (2015). Similarly, we were unable to confirm an association between small clones with TP53 mutation and poor survival (Rossi et al , 2014), assuming that small clones with TP53 mutation are comparable to our patients with FISH detectable but low percentages of 17p deletion.…”

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

“…Whilst it is optional to provide an estimation of the clone size for each separate abnormality reporting is encouraged where distinct sub clones are identified. This can be useful for follow up studies and may have clinical relevance in the future (Dal Bo et al, ; Marasca et al, ).…”

ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

“…Alternative possibilities that have been considered include deletion, mutation or epigenetic silencing of other genes either within or outside the MDR or the associated genomic complexity. 8,[21][22][23] Neither candidate gene sequencing nor whole exome sequencing studies have identified mutations within other genes located in the MDR. 24,25 However, recent data have revealed a high incidence of deletion or, more rarely, mutation of BIRC3, a negative regulator of noncanonical NFκB signaling located at 11q22.…”