TP53 mutation and survival in aggressive B cell lymphoma
TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the R...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
14 June 2017
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| In: |
International journal of cancer
Year: 2017, Jahrgang: 141, Heft: 7, Pages: 1381-1388 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.30838 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1002/ijc.30838 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.30838 
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| Verfasserangaben: | Thorsten Zenz, Markus Kreuz, Maxi Fuge, Wolfram Klapper, Heike Horn, Annette M. Staiger, Doris Winter, Hanne Helfrich, Jennifer Huellein, Martin-Leo Hansmann, Harald Stein, Alfred Feller, Peter Möller, Norbert Schmitz, Lorenz Trümper, Markus Loeffler, Reiner Siebert, Andreas Rosenwald, German Ott, Michael Pfreundschuh and Stephan Stilgenbauer |
| Zusammenfassung: | TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the RICOVER-60 trial. Of 1,222 elderly patients (aged 61-80 years) enrolled in the study and randomized to six or eight cycles of CHOP-14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index-Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B-symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event-free (EFS), progression-free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI-factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed. |
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| Beschreibung: | Gesehen am 26.07.2018 |
| Beschreibung: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.30838 |