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To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence  in situ  hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) ( P <0.0001). In the multivariate analysis, only the presence of 11q-L, mutated  IGHV  status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached ( P  = 0.008). The absence of splenomegaly ( P  = 0.02), low LDH ( P  = 0.018) or β2M ( P  = 0.006), and the presence of 11q-L ( P  = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the  ATM ,  TP53 ,  NOTCH1 ,  SF3B1 ,  MYD88 ,  FBXW7 ,  XPO1  and  BIRC3  genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50%  vs  94.1%,  P  = 0.023). In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes.

plos one

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia