Univariate and multivariate analysis of overall survival in adults with ALL.

<p>Univariate and multivariate analysis of overall survival in adults with ALL.</p

Characteristics of patients with ALL included in the study.

<p>Characteristics of patients with ALL included in the study.</p

Kaplan—Meier plots demonstrating the effect of copy number changes on overall survival (OS) in adult patients with ALL.

<p>(A) OS of the whole cohort of adults with ALL with respect to the presence of deletions in 17p. (B) OS of adults without poor-risk with respect to the presence of deletions in 7p12.2. (C) OS of adults with ALL classified in the poor-risk cytogenetic group with respect to the presence of deletions in 3q26.32. NR, not reached.</p

(A) Time to first therapy (TFT) and (B) overall survival (OS) of 197 patients with 11q deletion CLL and <40% or ≥40% FISH losses.

<p>(A) Time to first therapy (TFT) and (B) overall survival (OS) of 197 patients with 11q deletion CLL and <40% or ≥40% FISH losses.</p

Characteristics of 197 patients with 11q deletion with respect to the number of losses detected by FISH: <40% (n = 51) or ≥40% (n = 146).

<p>*Number of cases.</p><p>Characteristics of 197 patients with 11q deletion with respect to the number of losses detected by FISH: <40% (n = 51) or ≥40% (n = 146).</p

Multivariate Cox regression analysis of overall survival in 11q- CLL patients with respect to the number of losses detected by FISH: <40% (n = 51) or ≥40% (n = 146).^*

<p>*The following covariates were included in the final model: age, sex, Binet stage, splenomegaly, extended lymphadenopathies, LDH, β₂ microglobulin, CD38, ZAP70, <i>IGHV</i> mutation status and percentage 11q deleted nuclei.</p><p>Multivariate Cox regression analysis of overall survival in 11q- CLL patients with respect to the number of losses detected by FISH: <40% (n = 51) or ≥40% (n = 146).^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143073#t002fn001" target="_blank">*</a>}</p

Distribution of mutations of <i>ATM</i>, <i>SF3B1</i>, <i>NOTCH1</i>, <i>TP53</i>, <i>XPO1</i> and <i>BIRC3</i> among 11q- CLL patients with respect to the percentage of 11q- cells.

<p>In the heat maps, rows correspond to identical genes, and columns represent individual patients color-coded on the basis of gene status (white: wild type; grey: mutated gene).</p

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

<div><p>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 <i>in situ</i> 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) (<i>P</i><0.0001). In the multivariate analysis, only the presence of 11q-L, mutated <i>IGHV</i> 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 (<i>P</i> = 0.008). The absence of splenomegaly (<i>P</i> = 0.02), low LDH (<i>P</i> = 0.018) or β2M (<i>P</i> = 0.006), and the presence of 11q-L (<i>P</i> = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the <i>ATM</i>, <i>TP53</i>, <i>NOTCH1</i>, <i>SF3B1</i>, <i>MYD88</i>, <i>FBXW7</i>, <i>XPO1</i> and <i>BIRC3</i> 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% <i>vs</i> 94.1%, <i>P</i> = 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.</p></div