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C. Brieghel et al.
AB
Figure 3. Overall survival (OS) in patients from time of treatment. Stratifying patients with TP53 aberrations including del(17p) based on (A) variant allele fre- quencies (VAF) with 10% cut-off or (B) 1% and 10% cut-off. (C) Del(17p) versus subgroups with TP53 mutations without del(17p) [TP53mut w/o del(17p)] with 1% VAF cut-off is shown. Del(17p) status may reflect baseline if a second fluorescence in situ hybridization (FISH) was not performed at time of treatment. P-values indi- cated in tables within the panels.
Discussion
This study demonstrates that neither high nor low bur- den TP53muts at time of CLL diagnosis independently influenced OS or TFS in a consecutive cohort of newly diagnosed patients. However, patients with del(17p) at time of diagnosis had an inferior outcome. In addition, the subgroup of patients with TP53ab over 10% VAF among patients with IGHV-U status demonstrated inferior OS and TFS. At time of treatment, patients with sole TP53muts over 1% VAF had shorter OS, as had patients with del(17p).
In our study, del(17p) in newly diagnosed CLL was rare (2.4%), although still demonstrating a negative prognostic impact in accordance with our previous validation of CLL-IPI3 in a Danish nation-wide cohort.24 The majority of del(17p) patients were, as expected, also TP53 mutated.5 Although we demonstrate a similar prevalence of TP53 mutated patients and a similar distribution of variant allele frequencies, TP53muts without concomitant FISH posi-
tive for del(17p) were more frequent in newly diagnosed patients (10.7% using an LOD of 0.3%) compared to pre- vious publications.13,14,17 In particular, sole low burden TP53muts (7.2%) was highly prevalent, whereas the prevalence of patients with sole high burden TP53muts (3.4%) was similar to previous reports.13,14,17 Despite a high prevalence, and in contrast to reports by Rossi et al.,13 we could not demonstrate impact on OS of neither high nor low burden TP53muts without del(17p) in newly diag- nosed patients. Similar to our results, Stengel et al. demon- strated a better OS in newly diagnosed patients with TP53mut only compared to concomitant del(17p) and TP53mut, which may support the lack of impact on OS in our smaller cohort.17 Furthermore, Nadeu et al. reported no impact on time to treatment among newly diagnosed TP53 mutated patients compared to TP53wt patients.14 More prevalent high-risk factors with impact on early need of treatment observed across previous studies may also contribute to the different impact of TP53muts.13,14,17 For example, the previous studies included older patients
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