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Economic Evaluation of Fluticasone Propionate/Formoterol (FlutiformÂź) vs. Fluticasone/Salmeterol and Budesonide/Formoterol in Spain
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(A) Time to first therapy (TFT) and (B) overall survival (OS) of 197 patients with 11q deletion CLL and <40% or â„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 â„40% FISH losses.</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 â„40% (n = 146).<sup>*</sup>
<p>*The following covariates were included in the final model: age, sex, Binet stage, splenomegaly, extended lymphadenopathies, LDH, ÎČ<sub>2</sub> 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 â„40% (n = 146).<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143073#t002fn001" target="_blank">*</a></sup></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 â„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 ÎČ2M (<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
Multivariate Cox regression analysis of time to first therapy in 11q- CLL patients with respect to the number of losses detected by FISH: <40% (n = 51) or â„40% (n = 146).<sup>*</sup>
<p>*The following covariates were included in the final model: age, sex, Binet stage, splenomegaly, extended lymphadenopathies, LDH, ÎČ<sub>2</sub> microglobulin, CD38, ZAP70, <i>IGHV</i> mutation status and percentage 11q deleted nuclei.</p><p>Multivariate Cox regression analysis of time to first therapy in 11q- CLL patients with respect to the number of losses detected by FISH: <40% (n = 51) or â„40% (n = 146).<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143073#t002fn001" target="_blank">*</a></sup></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
Characteristics of 197 patients with 11q deletion with respect to the number of losses detected by FISH: <40% (n = 51) or â„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 â„40% (n = 146).</p