Universität zu Köln

Zenz, Thorsten, Eichhorst, Barbara, Busch, Raymonde, Denzel, Tina, Haebe, Sonja, Winkler, Dirk, Buehler, Andreas, Edelmann, Jennifer, Bergmann, Manuela, Hopfinger, Georg ORCID: 0000-0002-8321-1342, Hensel, Manfred, Hallek, Michael, Doehner, Hartmut and Stilgenbauer, Stephan (2010). TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. J. Clin. Oncol., 28 (29). S. 4473 - 4480. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

Purpose The precise prognostic impact of TP53 mutation and its incorporation into treatment algorithms in chronic lymphocytic leukemia (CLL) is unclear. We set out to define the impact of TP53 mutations in CLL. Patients and Methods We assessed TP53 mutations by denaturing high-performance liquid chromatography (exons 2 to 11) in a randomized prospective trial (n = 375) with a follow-up of 52.8 months (German CLL Study Group CLL4 trial; fludarabine [F] v F + cyclophosphamide [FC]). Results We found TP53 mutations in 8.5% of patients (28 of 328 patients). None of the patients with TP53 mutation showed a complete response. In patients with TP53 mutation, compared with patients without TP53 mutation, median progression-free survival (PFS; 23.3 v 62.2 months, respectively) and overall survival (OS; 29.2 v 84.6 months, respectively) were significantly decreased (both P<.001). TP53 mutations in the absence of 17p deletions were found in 4.5% of patients. PFS and OS for patients with 17p deletion and patients with TP53 mutation in the absence of 17p deletion were similar. Multivariate analysis identified TP53 mutation as the strongest prognostic marker regarding PFS (hazard ratio [HR] = 3.8; P<.001) and OS (HR = 7.2; P<.001). Other independent predictors of OS were IGHV mutation status (HR = 1.9), 11q deletion (HR = 1.9), 17p deletion (HR = 2.3), and FC treatment arm (HR = 0.6). Conclusion CLL with TP53 mutation carries a poor prognosis regardless of the presence of 17p deletion when treated with F-based chemotherapy. Thus, TP53 mutation analysis should be incorporated into the evaluation of patients with CLL before treatment initiation. Patients with TP53 mutation should be considered for alternative treatment approaches. J Clin Oncol 28:4473-4479. (C) 2010 by American Society of Clinical Oncology

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zenz, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Raymonde UNSPECIFIED UNSPECIFIED UNSPECIFIED Denzel, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Haebe, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Buehler, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Edelmann, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Hopfinger, Georg UNSPECIFIED orcid.org/0000-0002-8321-1342 UNSPECIFIED Hensel, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Doehner, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494342
DOI:	10.1200/JCO.2009.27.8762
Journal or Publication Title:	J. Clin. Oncol.
Volume:	28
Number:	29
Page Range:	S. 4473 - 4480
Date:	2010
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FLUDARABINE PLUS CYCLOPHOSPHAMIDE; GENOMIC ABERRATIONS; DISEASE PROGRESSION; 1ST-LINE THERAPY; DRUG-RESISTANCE; CD38 EXPRESSION; GENE-MUTATIONS; P53 MUTATIONS; ALEMTUZUMAB; INACTIVATION Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49434